phosphorus-radioisotopes and Lung-Neoplasms

Topics: Animals; Environmental Exposure; Humans; Iodine Radioisotopes; Lung Neoplasms; Neoplasms, Radiation-Induced; Nuclear Warfare; Phosphorus Radioisotopes; Plutonium; Polonium; Radioactive Hazard Release; Radioisotopes; Radium; Radon; Risk Factors; Thorium; Uranium

Topics: Bone Neoplasms; Contrast Media; Germany; Humans; Iodine Radioisotopes; Leukemia, Radiation-Induced; Liver Neoplasms; Lung Neoplasms; Mining; Neoplasms, Radiation-Induced; Pacific Islands; Paranasal Sinus Neoplasms; Phosphorus Radioisotopes; Polycythemia Vera; Radioactive Fallout; Radiotherapy; Radium; Radon; Spondylitis, Ankylosing; Thorium; Thorium Dioxide; Thyroid Neoplasms; United States; Uranium

In this early Phase II study, the authors investigated the efficacy of intratumoral injection of P-32 chromic phosphate in 17 patients with refractory solid tumors or solitary metastases in terms of response rates and overall survival.. Seventeen patients (median age, 60 years) with either cytostatic drug-resistant tumors or tumors known to be primarily chemotherapy-resistant were entered into the study. After sonographic determination of the tumor volume, P-32 chromic phosphate (74-555 MBq) was injected into the central part of the tumor under sonographic guidance. Follow-up investigations included serial scintigraphy, sonographic examinations, and hematologic studies.. Injection of P-32 chromic phosphate into refractory tumors resulted in remarkable regression. The median survival of all patients was 13 months (range, 8-25 months). The response rate was 71% (12 patients). A complete remission was seen in 7 patients (41%), and the rate of partial remissions was 29% (5 patients). However, 5 patients (30%) did not respond to the treatment. In one patient thrombocytopenia was observed, but no other side effects were apparent. Important pathologic and anatomic changes within the tumor tissue were demonstrated in solitary liver metastases of gastrointestinal malignancies excised in second-look operations. In all cases examined, formation of a cyst within the area of central activity, surrounded by a centrifugal necrotic ring and a marginal fibrotic structure, was found.. Lack of persistent systemic or local side effects, as well as noteworthy efficacy, are properties of this optimal regional treatment modality with P-32 chromic phosphate. This modality deserves consideration for further clinical trials.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Breast Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Chromium Compounds; Digestive System Neoplasms; Drug Resistance, Neoplasm; Female; Head and Neck Neoplasms; Humans; Injections, Intralesional; Lung Neoplasms; Male; Middle Aged; Neoplasms; Phosphates; Phosphorus Radioisotopes; Survival Rate

Malignant pericardial effusion is usually treated only when signs of cardiac tamponade develop. Several methods of treatment have been reported with an overall response rate of approximately 75%. Since our initial study using intrapericardial 32P-colloid instillation as a treatment modality for pericardial effusion demonstrated a significant higher response rate, this study was conducted to further evaluate the efficacy of intrapericardial 32P-colloid in terms of response rates and duration of remissions. Intrapericardial instillation of 185-370 MBq (5-10 mCi) 32P-colloid in 36 patients with malignant pericardial effusion resulted in a complete remission rate of 94.5% (34 patients) whereas two patients did not respond to treatment due to a foudroyant formation of pericardial fluid. The median duration time was 8 months. No side-effects were observed. These results suggest that intrapericardial instillation of 32P-colloid is a simple, reliable and safe treatment strategy for patients with malignant pericardial effusions. Therefore, since further evidence is provided that 32P-colloid is significantly more effective than external radiation or non-radioactive sclerosing agents, this treatment modality should be considered for the management of malignant pericardial effusion.

Topics: Breast Neoplasms; Cardiac Tamponade; Chromium Compounds; Female; Gastrointestinal Neoplasms; Humans; Instillation, Drug; Lung Neoplasms; Lymphoma; Neoplasms; Pericardial Effusion; Phosphorus Radioisotopes; Radiopharmaceuticals

The purpose of this study was to validate a previously reported body contour measurement using Compton backscatter sources with bremsstrahlung SPECT imaging.. Bremsstrahlung SPECT imaging was performed with 32P using a dual-headed camera system fitted with medium-energy, parallel-hole collimators. Two sources of 99mTc were placed directly on each collimator. Energy windows of 100 keV +/- 25% were used to image the 32P and also to record the Compton scatter from the 99mTc sources. Eleven patients enrolled in clinical Phase I therapeutic protocols were injected with 32P-chromic phosphate and SPECT images were acquired and reconstructed in the transaxial plane. The 32P distribution and the patient body contour were both visualized in these slices. The anteroposterior and lateral patient dimensions were measured by generating count profiles parallel to the anteroposterior and lateral body contour, respectively, at the midline in a transaxial slice. The distance in centimeters between the two centroids of each profile is representative of the anteroposterior and lateral dimensions and was determined for each patient. These anteroposterior and lateral dimensions were compared to the same distance measurements made in these patients by CT in an anatomically comparable transaxial slice. A cylindrical SPECT phantom was also studied to further validate the contour measurements.. The mean percent difference in the patient dimension measurements between SPECT and CT was -0.8% with a range of -8.5% to 9.9%. The percent difference between the known and SPECT measured dimensions in the cylindrical phantom was 0.5%.. The two external Compton scatter source method is accurate for determining the body contour.

Topics: Chromium Compounds; Head and Neck Neoplasms; Humans; Image Processing, Computer-Assisted; Liver Neoplasms; Lung Neoplasms; Pancreatic Neoplasms; Phantoms, Imaging; Phosphates; Phosphorus Radioisotopes; Scattering, Radiation; Technetium; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed

In the past, we have clinically evaluated radiolabelled antibodies in Hodgkin's disease and hepatocellular cancer. Increased tumour pressure, reduced vascularity and poor diffusion has limited significant radiolabelled antibody tumour dose deposition. Using intratumoural infusion of macroaggregated albumin to blockade exiting vasculature followed by colloidal chromic 32Phosphorous, we have been able to achieve 75% to 100% tumour dose deposition by interstitial tumour infusion under computerised tomographic guidance. Phase I studies in a variety of solid tumours indicate extremely high doses may be achieved without toxicity (i.e. non-resectable pancreas 900,000 cGy to 1.7 million cGy) with tumour control and remission. This is a review of those studies and how the technique was applied.

Topics: Astrocytoma; Brachytherapy; Brain Neoplasms; Carcinoma, Hepatocellular; Carcinoma, Small Cell; Chemoembolization, Therapeutic; Chromium; Colloids; Dexamethasone; Head and Neck Neoplasms; Hodgkin Disease; Humans; Injections, Intralesional; Liver Neoplasms; Lung Neoplasms; Pancreatic Neoplasms; Phosphorus Radioisotopes; Radiography, Interventional; Radioimmunotherapy; Radiotherapy Dosage; Remission Induction; Serum Albumin; Tomography, X-Ray Computed

Topics: Aged; Breast Neoplasms; Clinical Trials as Topic; Cyclophosphamide; Female; Fluorouracil; Humans; Lung Neoplasms; Male; Methotrexate; Middle Aged; Neoplasm Metastasis; Neoplasms; Phosphorus Radioisotopes; Remission, Spontaneous; Vincristine

The aim of this work is to evaluate the application of tissue-specific dose kernels instead of water dose kernels to improve the accuracy of patient-specific dosimetry by taking tissue heterogeneities into consideration.. Tissue-specific dose point kernels (DPKs) and dose voxel kernels (DVKs) for yttrium-90 (. The simulation results indicate that the highest differences between water and other tissue DPKs occur in bone for. A novel technique is proposed considering tissue-specific dose kernels in the dose calculation algorithm. This algorithm potentially enables patient-specific dosimetry and improves estimation of the average absorbed dose of

Topics: Algorithms; Bone Neoplasms; Computer Simulation; Humans; Liver Neoplasms; Lung Neoplasms; Lutetium; Monte Carlo Method; Organ Specificity; Phosphorus Radioisotopes; Radioisotopes; Radiometry; Radionuclide Imaging; Radiotherapy Planning, Computer-Assisted; Water; Yttrium Radioisotopes

The aim of this paper was to observe the metabolic mode of 32P at the level of sub-target nuclides.. Twenty-one cancer patients were locally injected with 32P-labelled glass microspheres and then observed to determine the equalization of 32P radionuclide metabolism in the tumor target. We imaged 3 sub-target regions of interest (ROI) 1/3 the size in both the anterior and posterior directions by bremsstrahlung single-photon emission computed tomography (SPECT) X-ray imaging. The radiation dose parameters of the beta rays including the initial dose rate, the effective half-life, and the effective half-life of the cumulative radiation dose were then calculated.. The radionuclide metabolism of the 21 complete tumor targets complied with the mono-compartmental model of index metabolism, but the level of tumor control did not correlate with radiation dose parameters. In contrast, the radionuclide metabolism of the 63 sub-targets did not comply with the mono-compartmental model. Instead, 32 sub-targets were better represented by bi-compartmental or tri-compartmental metabolic models. None of the remaining 31 sub-targets complied with index metabolism.. The complexity of the radiation dose at the sub-target level partially explains poor local tumor control. Future studies will be required to improve the expression of internal exposure to radiation dose parameters.

Topics: Adolescent; Adult; Aged; Carcinoma, Hepatocellular; Child; Female; Humans; Laryngeal Neoplasms; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Microspheres; Middle Aged; Neoplasms; Phosphorus Radioisotopes; Radiation Dosage; Rectal Neoplasms; Stomach Neoplasms; Tomography, Emission-Computed, Single-Photon; Young Adult

Lung cancer is the leading cause of cancer-related death. Among the new modalities to treat cancer, internal radiotherapy seems to be very promising. However, the achievable dose-rate is two orders of magnitude lower than the one used in conventional external radiotherapy, and data has to be collected to evaluate the cell response to highlight the potential effectiveness of low-dose-rate beta particles irradiation. This work investigates the phosphorus beta irradiation ((32)P) dose response on the clonogenicity of human A549 non-small cell lung adenocarcinoma cells and compares it to high-dose-rate X-irradiations results.. Cell survival was evaluated by a colony forming assay eight days after low-dose-rate (32)P beta irradiations (0.8 Gy/h) and high-dose-rate X-ray irradiations (0.855 Gy/min).. Survival curves were obtained for both types of irradiations, and showed hyper-radiosensitivity at very low doses. Radiosensitivity parameters were obtained by using the linear-quadratic and induced-repair models.. Comparison with high-dose-rate X-rays shows a similar surviving fraction, confirming the effectiveness of beta particles for tumor sterilization.

Topics: Adenocarcinoma; Adenocarcinoma of Lung; Beta Particles; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cell Survival; Dose-Response Relationship, Radiation; Humans; Lung Neoplasms; Phosphorus Radioisotopes; X-Rays

The purpose of this study was to investigate the therapy effects of intratumoral administration of (32)P-CP-PLLA particles in a rabbit VX2 lung tumor model.. 16 rabbits with tumors were randomly divided into 4 groups. 4 rabbits served as untreated controls, and others received intratumoral administration of (32)P-CP-PLLA particles with CT guidance. The total radioactivities in treated groups were as follows: a low activity was 93 MBq (n=4) (group 1), a medium activity was 185 MBq (n=4) (group 2) and a high activity was 370 MBq (n=4) (group 3). Brachytherapy treated VX2 tumors underwent (18)F-FDG PET/CT at 0 day, 3 day, 7 day and 14 day postinjection. In control group, (18)F-FDG PET/CT images were acquired at the same time points but without any treatment. Bremsstrahlung SPECT images were performed at 14 days after intratumoral brachytherapy in treated groups. After Bremsstrahlung SPECT and last (18)F-FDG PET/CT imagings, the rabbits were euthanized and the tumors were removed for histological examination.. Bremsstrahlung SPECT images study indicated that there was no leakage of (32)P out of the injection site at 14 days after treatment. Compared with the control, the tumor volumes in treated groups significantly decreased, and (32)P-CP-PLLA particle produced a reduction in maximum or mean SUV of VX2 tumor (p<0.05). The percentage changes in maximum and mean SUV gradually decreased in group 1 and group 2 from day 3 to day 14 (p<0.05). A transient increase in (18)F-FDG accumulation at group 3 occurred due to the inflammatory reaction elements. Activity dependence was seen in HE and PCNA staining after 14 days treatment among three treated groups (p<0.05).. Our data suggested that (32)P-CP-PLLA particle localized on the injecting sites. This novel brachytherapy device efficiently suppressed the growth of the VX2 tumors implanted in the rabbit.

Topics: Animals; Brachytherapy; Disease Models, Animal; Fluorodeoxyglucose F18; Lactic Acid; Lung Neoplasms; Phosphorus Radioisotopes; Polyesters; Polymers; Rabbits; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon; Treatment Outcome; Tumor Burden

³²P-chromic phosphate-poly (L-lactic) acid (³²P-CP-PLLA) microparticle is a novel potent brachytherapy implant, which has good biocompatibility and biodegradability. The aim of this study is to investigate the changes of pathology and PET/CT images in VX2 rabbit tumor after treatment with intratumorol administration of ³²P-CP-PLLA microparticles, and to explore the effects and influence of tumor growth and apoptosis related proteins in VX2 lung tumor treatment with ³²P-CP-PLLA microparticles.. Twenty-four tumor bearing rabbits were randomly divided into 4 groups (6 in each group). Group 1, 2 and 3 were treated groups; group 4 was the control. Under CT guidance, ³²P-CPPLLA microparticles were implanted into tumors. Low, medium and high treatment doses were 93 MBq (group 1), 185 MBq (group 2) and 370 MBq (group 3), respectively. ¹⁸F-FDG PET/CT was performed at d0, d3, d7 and d14 after intratumoral administration. In the control group, ¹⁸F-FDG PET/CT images were acquired at the same time points but without treatment. The standardized uptake value (SUV) of tumor regions were calculated. After last PET/CT imaging, the rabbits were euthanized and the tumors were removed for histological and immunohistochemical examination. The pathology and the expression of apoptosis related proteins (bcl-2, bax) were compared.. No significant difference of SUVmax was observed between the treatment groups and the control group at d0. At d14, the SUVmax values for group 1, 2 and 3 were 0.80±0.10, 1.1±0.19 and 2.85±0.15, respectively, and were significantly lower than that of the control group (5.61±0.50)(P < 0.05). Significant dose-response relationship was observed in SUVmax between group 1 and group 2, and the SUV values gradually decreased from d7 to d14 after treatment. In group 3, SUVmax gradually increased and reached a peak at d7 then significantly decreased. The SUVmax values of group 3 were significantly lower than those of the control at the same time point (P < 0.05). HE staining found degenerative necrosis at the site was nearby the microparticle. Necrosis became serious increasing with the radioactivity. Inflammatory cell infiltration was rarely seen in tumors treated with 93 MBq or 185 MBq ³²P-CP-PLLA microparticles. In contrast, the necrotic area was surrounded by marked inflammatory cell infiltration in group 3. IHC analysis showed that the expression of bcl-2 in treated groups were lower than those in the control group, and the expression of bax in treated group was higher than those in the control group (P < 0.05). The ratio of bcl-2/bax protein significantly decreased in the treated group (P < 0.05). Dose dependence was seen in the expression of apoptosis related proteins.. The sustained irradiation of ³²P-CP-PLLA microparticles can direct kill the VX2 tumor cell, thus the glycolysis of which were suppressed. Although the alive tumor cells still presented faraway from the microparticle, the expression of apoptosis related proteins in which were significantly different from the control. Bcl-2 and bax gene were induced to participate in regulation for the apoptosis of VX2 tumor cell by ionizing radiation from ³²P-CP-PLLA microparticles, so that the tumor growth was inhibited.

Topics: Animals; Apoptosis; Brachytherapy; Chromium Compounds; Disease Models, Animal; Female; Fluorodeoxyglucose F18; Humans; Lung Neoplasms; Male; Phosphates; Phosphorus Radioisotopes; Positron-Emission Tomography; Rabbits; Random Allocation; Tomography, X-Ray Computed

Benzo[a]pyrene (B[a]P) is a potent human and rodent lung carcinogen. This activity has been ascribed in part to the formation of anti-trans-7,8-dihydroxy-7,8-dihydroB[a]P-9,10-epoxide (BPDE)-DNA adducts. Other carcinogenic mechanisms have been proposed: (1) the induction of apurinic sites from radical cation processes, and (2) the metabolic formation of B[a]P-7,8-quinone (BPQ) that can form covalent DNA adducts or reactive oxygen species which can damage DNA. The studies presented here sought to examine the role of stable BPQ-DNA adducts in B[a]P-induced mouse lung tumorigenesis. Male strain A/J mice were injected intraperitoneally once with BPQ or trans-7,8-dihydroxy-7,8-dihydroB[a]P (BP-7,8-diol) at 30, 10, 3, or 0mg/kg. Lungs and livers were harvested after 24h, the DNA extracted and subjected to (32)P-postlabeling analysis. Additional groups of mice were dosed once with BPQ or BP-7,8-diol each at 30 mg/kg and tissues harvested 48 and 72 h later, or with B[a]P (50mg/kg, a tumorigenic dose) and tissues harvested 72 h later. No BPQ or any other DNA adducts were observed in lung or liver tissues 24, 48, or 72 h after the treatment with 30 mg/kg BPQ. BP-7,8-diol gave BPDE-DNA adducts at all time points in both tissues and B[a]P treatment gave BPDE-DNA adducts in the lung. In each case, no BPQ-DNA adducts were detected. Mouse body weights significantly decreased over time after BPQ or BP-7,8-diol treatments suggesting that systemic toxicity was induced by both agents. Model studies with BPQ and N-acetylcysteine suggested that BPQ is rapidly inactivated by sulfhydryl-containing compounds and not available for DNA adduction. We conclude that under these treatment conditions BPQ does not form stable covalent DNA adducts in the lungs or livers of strain A/J mice, suggesting that stable BPQ-covalent adducts are not a part of the complex of mechanisms involved in B[a]P-induced mouse lung tumorigenesis.

Topics: 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; Acetylcysteine; Animals; Benzo(a)pyrene; Carcinogens; DNA Adducts; Free Radical Scavengers; Humans; Lung Neoplasms; Male; Mice; Mice, Inbred A; Models, Biological; Phosphorus Radioisotopes; Polycyclic Aromatic Hydrocarbons

3-Nitrobenzanthrone (3-NBA) is a potent mutagen and potential human carcinogen identified in diesel exhaust and ambient air particulate matter. Previously, we detected the formation of 3-NBA-derived DNA adducts in rodent tissues by 32P-postlabeling, all of which are derived from reductive metabolites of 3-NBA bound to purine bases, but structural identification of these adducts has not yet been reported. We have now prepared 3-NBA-derived DNA adduct standards for 32P-postlabeling by reacting N-acetoxy-3-aminobenzanthrone (N-Aco-ABA) with purine nucleotides. Three deoxyguanosine (dG) adducts have been characterised as N-(2'-deoxyguanosin-8-yl)-3-aminobenzanthrone-3'-phosphate (dG3'p-C8-N-ABA), 2-(2'-deoxyguanosin-N2-yl)-3-aminobenzanthrone-3'-phosphate (dG3'p-N2-ABA) and 2-(2'-deoxyguanosin-8-yl)-3-aminobenzanthrone-3'-phosphate (dG3'p-C8-C2-ABA), and a deoxyadenosine (dA) adduct was characterised as 2-(2'-deoxyadenosin-N6-yl)-3-aminobenzanthrone-3'-phosphate (dA3'p-N6-ABA). 3-NBA-derived DNA adducts formed experimentally in vivo and in vitro were compared with the chemically synthesised adducts. The major 3-NBA-derived DNA adduct formed in rat lung cochromatographed with dG3'p-N2-ABA in two independent systems (thin layer and high-performance liquid chromatography). This is also the major adduct formed in tissue of rats or mice treated with 3-aminobenzanthrone (3-ABA), the major human metabolite of 3-NBA. Similarly, dG3'p-C8-N-ABA and dA3'p-N6-ABA cochromatographed with two other adducts formed in various organs of rats or mice treated either with 3-NBA or 3-ABA, whereas dG3'p-C8-C2-ABA did not cochromatograph with any of the adducts found in vivo. Utilizing different enzymatic systems in vitro, including human hepatic microsomes and cytosols, and purified and recombinant enzymes, we found that a variety of enzymes [NAD(P)H:quinone oxidoreductase, xanthine oxidase, NADPH:cytochrome P450 oxidoreductase, cytochrome P450s 1A1 and 1A2, N,O-acetyltransferases 1 and 2, sulfotransferases 1A1 and 1A2, and myeloperoxidase] are able to catalyse the formation of 2-(2'-deoxyguanosin-N2-yl)-3-aminobenzanthrone, N-(2'-deoxyguanosin-8-yl)-3-aminobenzanthrone and 2-(2'-deoxyadenosin-N6-yl)-3-aminobenzanthrone in DNA, after incubation with 3-NBA and/or 3-ABA.

Topics: Adenine; Animals; Benz(a)Anthracenes; DNA Adducts; Female; Guanine; Lung; Lung Neoplasms; Phosphorus Radioisotopes; Rats; Rats, Sprague-Dawley; Vehicle Emissions

We report our experience in the use of radionuclides in the treatment of bone metastases in patients with various primary cancers: breast cancer, prostate cancer, lung cancer, etc.. Eighty-seven patients (53 women, 34 men) with bone metastases were treated for pain relief with either 32-P (71 patients) or 89-Sr (16 patients). Fifty-three of the patients had breast cancer, 27--rostate cancer, 6--lung cancer and 1--kidney cancer. The patients were examined for side effects when 32-P was administered perorally and 89-Sr injected intravenously. We also studied the changes in the levels of hemoglobin, white blood cells (WBCs) count and platelets count.. We found a significant decrease in the WBC and platelet count in the patients treated with 32-P (U = 2.20, P < 0.05 and U = 4.57, P < 0.001) one month after the therapy. These parameters showed no significant decrease in the group treated with 89-Sr. The pain, which was the rationale to use the radioactive isotopes, was relieved and the patients restored their previous mobility.. The fact that 32-P alleviated the grave symptom of pain at the relatively weak radiation dose used (2 mCi) is a strong indication that this radiopharmaceutical can be used successfully for such a purpose, although some authors argue against its use in view of the myelosuppresion it causes. This myelosuppression, however, is mild and transient even without treatment and patients could benefit from this adjuvant treatment to manage the pain syndrome. 89-Sr administered intravenously in a dose of 4mCi also relieves pain efficiently but its use is limited by the cost of the quantity needed for 1 patient and for a single dose. The National Health Insurance Fund currently reimburses for a very limited quantity of this substance which makes the cost of the procedure 15 times as expensive as that using radioactive phosphorus.. Using the radiopharmaceuticals 32-P and 89-Sr provides an additional, easy and efficacious means for palliation of cancer patients with bone metastases, especially those who are refractory to percutaneous irradiation.

Topics: Bone Neoplasms; Breast Neoplasms; Female; Humans; Leukocyte Count; Lung Neoplasms; Male; Pain; Pain Measurement; Phosphorus Radioisotopes; Platelet Count; Prostatic Neoplasms; Strontium Radioisotopes; Treatment Outcome

Smoking is a major risk factor for lung cancer. This comparative study of smoking-related carcinogen-DNA adducts in pulmonary tissues and peripheral blood lymphocytes aims to further explore the primary DNA damaging processes by cigarette smoke in target and surrogate tissues. Samples of tumour and normal peripheral lung tissue, normal bronchial tissue and peripheral blood lymphocytes were obtained from a total of 85 lung cancer patients who underwent lung resection. Bulky DNA adducts were determined by 32P-postlabelling, and polycyclic aromatic hydrocarbon (PAH)-DNA adducts were detected by (+/-)-7beta, 8alpha-dihydroxy-9alpha,10alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene-DNA chemiluminescence immunoassay (BPDE-DNA CIA) in smaller subsets of tissue samples subject to availability of DNA. Bulky DNA adduct levels ranged between 0.3 and 27.8 adducts/10(8) nucleotides (nt) with mean adduct levels between 2.8 and 11.5 adducts/10(8) nt. Mean PAH-DNA adduct levels were 2.6-6.2 adducts/10(8) nt. Significantly higher bulky DNA adduct levels were detected in smokers' lungs as compared with non-smokers' (P < 0.02). PAH-DNA adduct levels appeared higher in the lungs of smokers compared with non-smokers but the difference was not significant. Lung tumour contained on average a 50% lower DNA adduct level compared with normal lung tissue. A statistically significant positive correlation was found between the DNA adduct levels of the corresponding tumour and normal lung tissue samples in both smokers and non-smokers using both methodologies. Bulky DNA adduct levels in normal lung and blood lymphocytes correlated significantly in non-smokers only (r = 0.55, P = 0.023). In lung tumour DNA samples there was a weak correlation between values obtained by 32P-postlabelling and by the BPDE-DNA immunoassay (r = 0.27, P = 0.054). However, with normal lung DNA samples, values obtained by the two assays did not correlate.

Topics: Adult; Aged; Bronchi; DNA Adducts; Female; Humans; Immunoassay; Lung; Lung Neoplasms; Lymphocytes; Male; Middle Aged; Phosphorus Radioisotopes; Smoking

N7-Methylguanine (N7-MeG) DNA adducts are markers of human exposure to methylating agents including tobacco-specific nitrosamines (TSNAs). Repair of this adduct is poor, so levels in lung tissue should reflect variation in both intensity of exposure and in metabolism. N7-MeG adducts in lung DNA from bronchial lavage samples were measured to determine whether levels were higher in smokers than non-smokers, and if levels were modified by genetic variation in carcinogen-metabolising enzymes. Adducts were detected in 38 out of 44 DNA samples by 32P post-labelling of the N7-methyldeoxyguanosine-3'-monophosphate (N7-MedGp) isolated from DNA digests by two-stage HPLC. N7-MeG adduct levels were higher in smokers than in never smokers ((9.99 +/-20.3)x10(-7) versus (0.58+/-0.50)x10(-7) N7-MedGp/deoxyguanosine-3'-monophosphate (dGp); P=0.02) and intermediate in ex-smokers ((5.59+/-15.6)x10(-7) N7-MedGp/dGp). Adduct levels tended to be higher in individuals with GSTM1 null, GSTT1 null or GSTP1 ile/ile genotypes. When genotypes were combined, N7-MedGp levels among GSTM1 null/GSTT1 null individuals (n=6) were higher than among those having at least one wild-type allele of these two genes ((26.1+/-38.0)x10(-7) versus (2.73+/-4.07)x10(-7) N7-MedGp/dGp), although the results were not statistically significant (P=0.13). Adduct levels were highest in individuals with three unfavourable genotypes (GSTM1 null/GSTT1 null and GSTP1 ile/ile) compared with others ((74.5+/-13.1)x10(-7) versus (2.64+/-3.89)x10(-7) N7-MedGp/dGp, P=0.02). N7-MeG adduct levels in DNA isolated from lung tissue thus reflect exposure to cigarette smoke, and genetic variation in carcinogen-metabolising enzymes may modify these levels.

Topics: Adult; Bronchoalveolar Lavage Fluid; Chromatography, High Pressure Liquid; Deoxyguanine Nucleotides; DNA Adducts; Genetic Variation; Genotype; Glutathione Transferase; Guanine; Humans; Lung Neoplasms; Phosphorus Radioisotopes; Smoking

Epidemiologic studies indicate that prolonged exposure to high pollution levels is associated with increased risk of cancer, especially lung cancer. However, under conditions of moderate or low air pollution, epidemiologic evidence does not permit reliable conclusions. Biomarker-based population studies may serve as complementary tools providing a better understanding of the relative contribution of ambient atmospheric pollution to the overall genotoxic burden suffered by city dwellers. However, past efforts to apply biomarkers to studies of low levels exposure to urban air pollution have given inconclusive results, partly because of the absence of adequate data on personal exposure, covering a time-window which is appropriate for the biomarkers being examined, as well as a battery of biomarkers reflecting different stages of the carcinogenic process. In the present paper, the potential of biomarker-based population studies to aid the assessment of the genotoxic and carcinogenic effects of urban air pollution is reviewed by reference to the achievements and limitations of earlier reported studies. The design and methodology adopted in a recently completed large-scale population study, carried out in the context of the European Union Environment and Climate Programme, known by the short name of AULIS project, is discussed and descriptive statistics of the main findings of the project are presented. These findings indicate that for cohorts suffering moderate-to-low exposures to airborne particulate-bound polycyclic aromatic hydrocarbons (PAHs), no simple correlation with biomarkers of genotoxicity existed and suggest that additional factors made a significant contribution to the overall genotoxic burden.

Topics: Adolescent; Adult; Air Pollutants; Air Pollution; Biomarkers; DNA; DNA Adducts; Environmental Illness; Female; Greece; Humans; Hypoxanthine Phosphoribosyltransferase; Inhalation Exposure; Lung Neoplasms; Lymphocytes; Male; Molecular Epidemiology; Mutagens; Mutation; Phosphorus Radioisotopes; Polycyclic Aromatic Hydrocarbons; Polymorphism, Genetic; Sister Chromatid Exchange; Urban Health; Urban Population

Lung cancer is the most common cause of cancer death among women in Taiwan. Epidemiological studies of lung cancer in Chinese women indicate that factors other than cigarette smoking are related to lung cancer risk. One such factor may be exposure to carcinogens formed during the cooking of food. The carcinogenic compounds in oil smoke particulates from Chinese cooking practice have not yet been characterized. To reveal the relationship between the high mortality rate of lung cancer in Chinese women and exposure to cooking oil fumes (COF), DNA adduct formation, induced by COF collected from frying fish under domestic conditions, was assessed in human lung adenocarcinoma CL-3 cell lines using the (32)P-postlabeling assay. DNA adduct levels were induced by COF in CL-3 cells in a dose-dependent manner. DNA adducts with a diagonal radioactive zone (DRZ) were observed when CL-3 cells were treated with COF. Surprisingly, only one spot of the DNA adduct profile was in the DRZ. The DNA adduct was analyzed by HPLC coupled with an on-line radioactive detector. The retention time of the major DNA adduct corresponded to that of authentic benzo[a]pyrene 7,8-diol 9, 10-epoxide N2-deoxyguanonsine (BPDE-N2-dG). Moreover, the mass spectrum of the major DNA adduct in CL-3 cells was confirmed to be BPDE-N2-dG by liquid chromatography/mass spectrometry. In conclusion, BPDE-N2-dG adduct formation in human lung cells supports epidemiological findings of an association between cooking fume exposure and lung cancer in Chinese women.

Topics: 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; Adenocarcinoma; Air; Carcinogens; Chromatography, High Pressure Liquid; Cooking; Deoxyguanosine; DNA Adducts; Humans; Isotope Labeling; Lung Neoplasms; Mass Spectrometry; Oils; Phosphorus Radioisotopes; Polycyclic Aromatic Hydrocarbons; Tumor Cells, Cultured

Infusional brachytherapy for treatment of neoplasms, with colloidal 32P has been used to treat various tumors in the pancreas, liver, brain, lung, and head and neck. In performing such treatments, anatomical verification of the location of the administered 32P from the image obtained by Bremsstrahlung SPECT alone is not possible due to the lack of internal landmarks, since the radionuclide is distributed only in the tumor and does not usually accumulate in the normal organs. The purpose of this study was to provide a practical three-dimensional approach for image fusion between Bremsstrahlung SPECT and CT.. The tumors in four cancer patients were injected directly with 32P under CT guidance. A Bremsstrahlung SPECT study using 99mTc backscatter sources to obtain the body contour was then performed. SPECT images were used to generate the skin contours using a threshold detection method. A three-dimensional surface was generated from these contours using a tiling program and fused with a corresponding CT surface generated from a CT scan in the same patient through an iterative surface-fitting algorithm. The three-dimensional surface of the region of high-activity, corresponding to the infused tumor, was then generated using the Bremsstrahlung SPECT data by mapping the iso-count surfaces through a computer program. The three-dimensional image of the organ then was fused with the registered CT-SPECT datasets.. The accuracy of fit measured as the mean distance between the SPECT and CT surfaces was in the range of 3-4 mm.. The anatomical co-registration of Bremsstrahlung SPECT with CT images using the outer surface-fitting algorithm is a reliable tool. This correlation permits direct anatomic confirmation of the region of the 32P activity distribution with the anatomic site selected for injection.

Topics: Algorithms; Brachytherapy; Humans; Kidney Neoplasms; Liver Neoplasms; Lung Neoplasms; Pancreatic Neoplasms; Phosphorus Radioisotopes; Radiotherapy Planning, Computer-Assisted; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed

Children with pulmonary sarcomas who have diffuse contamination of the pleural cavity present a difficult management problem for the radiation oncologist. Doses required to control even microscopic disease exceed lung tolerance. We report on the use of intracavity colloid P-32 in an attempt to treat the pleural surface and spare normal lung parenchyma and tissues of the chest wall. Three children--18 months, 12 years, and 3 years of age--had spillage of pulmonary sarcomas into the chest cavity. All children were treated with systemic chemotherapy. Initially, 0.5 mCi of technetium sulfur colloid (99mTc-sulfur colloid) was instilled into the pleural space to ascertain even distribution of isotope. This was then followed by installation of 5.0 mCi of colloidal P-32. Uniform distribution was then confirmed by bremsstrahlung scanning. All three patients are in complete remission 3.5 years, 3 years, and 1 year after treatment, respectively. The major toxicity was asymptomatic pleural thickening, which could be confused with disease. This was confirmed histologically to be fibrous in the first patient. The process diminished or stabilized with time in all 3 patients over the period of observation. In this small series, intrapleural colloidal P-32 appeared to be safe and well tolerated and would be expected to be less toxic than wide-field external beam in the treatment of spilled pulmonary sarcomas.

Topics: Child; Child, Preschool; Colloids; Humans; Infant; Injections, Intralesional; Lung Neoplasms; Male; Phosphorus Radioisotopes; Pleural Neoplasms; Radionuclide Imaging; Radiopharmaceuticals; Remission Induction; Respiratory Function Tests; Sarcoma

The results of radiphosphotherapy in 20 patients with iodine-negative metastases of thyroid cancer in the lung and bones have been analyzed. The treatment was carried out in two stages: radical surgery and 32P therapy of metastases. A dose of 100-185 MBq of the radionuclide was administrated weekly (total dose-300-700 MBq). As a result, improvement in treating stage IV thyroid tumor was registered.

Topics: Adult; Aged; Bone Neoplasms; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Phosphorus Radioisotopes; Radiotherapy Dosage; Thyroid Neoplasms; Treatment Outcome

Two rat osteosarcoma cell lines, YROS-1 and YROS-2, were established from two experimental osteosarcomas and induced by internal irradiation with radioactive phosphorus. Both cell lines formed a monolayer cell sheet in vitro with focal piling. The YROS-1 cells were refractile and spindle or polygonal in shape, whereas the YROS-2 cells were flat, spread and polygonal in shape. Ultrastructurally, the YROS-1 cells had well-developed rough-surfaced endoplasmic reticulum with focal pericellular deposition of calcified matrix, whereas YROS-2 had abundant polysomes and intracytoplasmic filaments. Both cell lines grew stably with population doubling times of 23 and 39 h, respectively. Flow cytometry revealed that YROS-1 was rich in proliferating cells compared to YROS-2, with a higher colony-forming efficiency. YROS-1 showed high alkaline phosphatase activity, while YROS-2 possessed low activity. When subcutaneously transplanted into lumbodorsal area of athymic nude mice, only YROS-1 formed tumors with frequent lung metastasis.

Topics: Animals; Cell Division; Female; Injections, Intraperitoneal; Lung Neoplasms; Mice; Mice, Nude; Neoplasm Transplantation; Osteosarcoma; Phosphorus Radioisotopes; Rats; Rats, Wistar; Tumor Cells, Cultured

The induction of DNA adducts and adenomas in the lungs of strain A/J mice has been investigated following the single i.p. administration of each of the following polycyclic aromatic hydrocarbons (PAH): pyrene, dibenz[a,h]anthracene, benzo[a]pyrene, benzo[b]fluoranthene, 5-methylchrysene, and cyclopenta[c,d]pyrene. DNA adducts were measured by 32P-postlabeling at times between 1 and 21 days following injection, while adenomas were counted at 240 days after treatment. Pyrene did not induce either DNA adducts or lung adenomas at any of the doses examined. Each of the remaining PAH induced both adenomas and DNA adducts in a dose-dependent manner, with dibenz[a,h]anthracene > 5-methylchrysene > cyclopenta[c,d]pyrene > benzo[a]pyrene > benzo[b]fluoranthene. DNA adducts reached maximal levels between 3 and 9 days after injection, followed by a gradual decrease. The time-integrated DNA adduct level (TIDAL) was calculated by numerically integrating the areas under the adduct persistence curves extrapolated to 240 days for each PAH at each dose level. This value represents the effective total molecular dose of PAH that was delivered to the lung DNA over the entire course of tumorigenesis. A strong correlation of lung adenoma induction with the TIDAL values was observed for each PAH. The slopes of the tumors versus TIDAL value relationships were essentially identical for 5-methylchrysene, cyclopenta[cd]pyrene, benzo[a]pyrene, and benzo[b]fluoranthene. The slope of this relationship for dibenz[a,h]anthracene was markedly greater. The essentially identical induction of adenomas as a function of TIDAL values for these PAH suggests that the formation and persistence of DNA adducts determines their carcinogenic potency.

Topics: Adenoma; Animals; Caprylates; DNA Adducts; Injections, Intraperitoneal; Lung; Lung Neoplasms; Male; Mice; Mice, Inbred A; Phosphorus Radioisotopes; Polycyclic Compounds; Time Factors; Triglycerides

A new fluorometric assay was validated for quantification of benzo[a]pyrene diolepoxide (BPDE)-DNA adducts in white blood cells (WBC) from humans exposed to polycyclic aromatic hydrocarbons (PAH). This assay has a detection limit of 2 pg of r-7,c-10,t-8,t-9-tetrahydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene derived from acid hydrolysis of BPDE-DNA, and can measure 1 BPDE adduct per 10(8) unmodified nucleotides. The quantity of WBC DNA required depends on the modification level and varies between 5 and 500 micrograms. The assay was applied to seven WBC DNA samples from lung cancer patients, six of whom were heavy smokers, and to three WBC DNA samples from healthy subjects employed in an aluminum production plant. High levels of BPDE-DNA adducts, ranging from 62 to 533 adducts/10(8) nucleotides were found in six out of seven DNA samples from the lung cancer patients. In WBC DNA from healthy persons BPDE-DNA adducts were detected only in two non-smokers, but at a much lower level than in lung cancer patients (4-10 adducts/10(8) nucleotides). Using coded WBC DNA samples, BPDE-DNA adduct levels measured by fluorometry of the B[a]P-tetrols, were compared with the results obtained by 32P-postlabeling (nuclease P1 enrichment) and ELISA measurements. A good correlation and proportionality was found between the levels of BPDE-DNA adducts measured by fluorometry and 32P-postlabeling (r = 0.95, P < 0.001, n = 8). The correlation between fluorometry and ELISA was much lower and not significant (r = 0.61, P = 0.1, n = 6). Moreover, the ELISA grossly overestimated BPDE-DNA adduct levels measured by the other two methods. The results demonstrate that the highly sensitive and specific fluorometric assay is suitable for measuring BPDE-DNA adducts in WBC from humans exposed to benzo[a]pyrene.

Topics: Benzo(a)pyrene; Benzopyrenes; Chromatography, High Pressure Liquid; DNA; DNA Adducts; Enzyme-Linked Immunosorbent Assay; Fluorescence; Humans; Leukocytes; Lung Neoplasms; Phosphorus Radioisotopes; Sensitivity and Specificity

Aromatic DNA adduct levels were determined in macroscopically normal bronchial tissues from 98 patients undergoing pulmonary surgery. The mean DNA adduct level for the 45 current smokers was significantly higher than that of the 16 life-time non-smokers. There was a weak association between adduct levels and daily cigarette consumption above 10 cigarettes per day. DNA adduct levels in the 37 former smokers suggested an exponential form of adduct elimination with a rapid initial and a slower later phase after cessation of smoking. There was no quantitative association between bronchial DNA adduct levels and lung cancer.

Topics: Adult; Aged; Autoradiography; Bronchi; DNA; DNA Damage; DNA, Neoplasm; Female; Humans; Lung Neoplasms; Male; Middle Aged; Phosphorus Radioisotopes; Smoking

Carcinogen-DNA adduct levels in lung parenchyma (surgical specimens) and urothelial (exfoliated) cells of smokers, ex-smokers and non-smokers were investigated. DNA adducts were analysed by 32P-postlabelling and levels were compared with tissue-specific activity of cytochrome P450-related enzymes, or whenever possible, with metabolic phenotypes and other macromolecular adducts. Lung cancer patients who were recent smokers had significantly induced benzo[a]pyrene (BaP)-3-hydroxylase (AHH) and ethoxycoumarin O-deethylase activities in lung parenchyma compared with smoking non-cancer patients. Pulmonary AHH activity showed a good correlation with the intensity of immunohistochemical staining for P4501A(1). In lung cancer patients from Italy and Finland who were recent smokers, lung AHH activity was positively correlated (r approximately 0.65; p < 0.001) with bulky DNA adduct levels. In some lung DNA samples from smokers, the level of BaP-diol-epoxide adducts determined by HPLC with fluorescence detection showed significant positive correlation with lung AHH activity and bulky DNA adduct levels. Molecular dosimetry studies provided evidence that aromatic amines such as 4-aminobiphenyl (ABP) in tobacco smoke are primarily responsible for bladder cancer in smokers. The N-(deoxyguanosin-8-yl)-4-ABP adduct was the major smoking-related adduct in DNA of bladder biopsies from bladder cancer patients and in the DNA of exfoliated urothelial cells of smoking volunteers. The adduct levels of ABP with haemoglobin and with deoxyguanosine in urothelial DNA (determined by 32P-postlabelling) were linearly and significantly correlated, and both were related to recent cigarette smoking. Metabolic phenotype (fast/slow N-acetylator and N-oxidizer) significantly affected the levels of ABP-haemoglobin adducts.

Topics: Aryl Hydrocarbon Hydroxylases; Biomarkers; Carcinogens; Cytochrome P-450 CYP1A1; Cytochrome P-450 Enzyme System; DNA; DNA Damage; Humans; Lung; Lung Neoplasms; Oxidoreductases; Phenotype; Phosphorus Radioisotopes; Smoking; Urinary Bladder

An improved high-performance liquid chromatography/fluorometric assay has been established to quantitate the benzo(a)pyrene (BP) tetrols released after acid hydrolysis of lung DNA from lung cancer patients, so that the formation of benzo(a)pyrene diol-epoxide-DNA adducts can be measured. The r-7,c-10,t-8,t-9-tetrahydroxy-7,8,9,10-tetrahydro-BP isolated by high-performance liquid chromatography was determined by chromatography in two different solvent systems and fluorescence spectroscopy. This assay has a detection limit of 2 pg of r-7,c-10,t-8,t-9-tetrahydroxy- 7,8,9,10-tetrahydro-BP, requires 100-500 micrograms of DNA, and can measure 1 adduct/10(8) unmodified nucleotides. As this assay does not use immunoaffinity chromatography or solvent extraction, it allows a > 90% recovery of benzo(a)pyrene diol-epoxide-DNA adducts. This procedure has been tested on 13 DNA samples prepared from nontumorous lung parenchyma taken from lung cancer patients at surgery and revealed the presence of DNA adducts of the anti-benzo(a)pyrene diol-epoxide in 9 of 11 samples from smokers and in 2 of 2 ex-smokers. In only two samples from smokers the formation of adducts derived from syn-benzo(a)pyrene diol-epoxide was detected. A 15-fold variation in DNA adduct level was found in 11 of 13 DNA samples, with a range of 0.6-9.9 adducts of benzo(a)pyrene diol-epoxide/10(8) nucleotides. In samples containing both anti- and syn-benzo(a)pyrene diolepoxide-DNA adducts, the anti/syn adduct ratio is 2:1. A highly significant correlation was found between pulmonary microsomal aryl hydrocarbon hydroxylase activity and the level of benzo(a)pyrene diolepoxide-DNA adduct (r = 0.91; P < 0.001; n = 13). A crude linear correlation between the amounts of these adducts and those of bulky DNA adducts determined by 32P-postlabeling assay was observed in the same samples (r = 0.78; P < 0.02; n = 13). Thus this highly sensitive and specific procedure is suitable for measuring benzo(a)pyrene diolepoxide-DNA adducts in human tissues from environmentally exposed subjects and could be adapted to measure polycyclic aromatic hydrocarbons other than BP.

Topics: 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; Adult; Aged; Animals; Aryl Hydrocarbon Hydroxylases; Benzo(a)pyrene; Cattle; Chromatography, High Pressure Liquid; DNA; DNA Adducts; Fluorometry; Genetic Variation; Humans; Hydrolysis; Isotope Labeling; Lung; Lung Diseases; Lung Neoplasms; Male; Microsomes; Middle Aged; Phosphorus Radioisotopes; Radiometry; Smoking; Thymus Gland

Analogues of somatostatin (SS) and luteinizing hormone-releasing hormone (LH-RH) activate tyrosine phosphatases in MIA PaCa-2 human pancreatic cancer cell line membranes and inhibit growth. We compared the substrates phosphorylated by epidermal growth factor (EGF) to those dephosphorylated by the SS analogue RC-160 (D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2) and [D-Trp6]LH-RH in cancer cell lines such as MIA PaCa-2 (human pancreatic cancer), HCPC (hamster cheek pouch carcinoma), A-549 (human lung cancer), HT-29 (human colon cancer), and R3230AC (breast cancer). EGF phosphorylated proteins of 170, 65, and 60 kDa and analogues of SS and LH-RH promoted the dephosphorylation of these proteins in MIA PaCa-2 and HCPC cell lines. The EGF receptor is 170 kDa. pp60src (60 kDa) is known to be a substrate for EGF receptor. The LH-RH receptor is also 60 kDa. The effects of RC-160 and [D-Trp6]LH-RH were quantitatively different. Examinations of HT-29, A-549, and R3230AC cancer cell lines revealed no phosphorylation by EGF or dephosphorylation by RC-160 and [D-Trp6]LH-RH. In addition to the 170-, 65-, and 60-kDa proteins, 35-kDa proteins were also phosphorylated in some cancer cell lines. This work demonstrates that analogues of SS and LH-RH can reverse the effects of EGF biochemically as well as functionally.

Topics: Amino Acid Sequence; Animals; Antineoplastic Agents; Autoradiography; Breast Neoplasms; Cell Line; Colonic Neoplasms; Epidermal Growth Factor; Gonadotropin-Releasing Hormone; Humans; Kinetics; Lung Neoplasms; Membrane Proteins; Molecular Sequence Data; Pancreatic Neoplasms; Phosphorus Radioisotopes; Phosphorylation; Protein Kinases; Protein-Tyrosine Kinases; Somatostatin; Triptorelin Pamoate; Tyrosine

The treatment of primary proliferative polycythaemia (polycythaemia rubra vera) may include radioactive phosphorus (P32) in conjunction with venesection. Acute leukaemia or carcinoma can be associated with the use of P32. We present a case of primary proliferative polycythaemia treated by repeat venesection together with P32 whose follow-up was complicated by the development of malignant neuroblastoma.

Topics: Bloodletting; Humans; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Neuroblastoma; Phosphorus Radioisotopes; Polycythemia Vera

In order to compare pulmonary DNA adducts and aryl hydrocarbon hydroxylase (AHH) activity, we have measured these two parameters in non-neoplastic surgical lung parenchymal samples from four ex-smokers and 19 smokers, out of 20 patients operated for lung cancer, and three for nonmalignant lung diseases. DNA adducts were determined by scintillation counting after 32P-postlabelling analysis. The microsomal fractions of the same lung specimen were assayed for AHH activity by a fluorometric method. Autoradiograms of DNA adducts found in lungs of smokers revealed two distinct diagonal radioactive zones that were absent in ex-smokers. The smokers had significantly higher levels (1.68-13.4 DNA adducts/10(8) nucleotides; mean +/- SD 5.38 +/- 3.19) than ex-smokers (0.23-2.21; 1.09 +/- 0.84). AHH activity in smokers ranged from 0.01 to 0.69 pmol/min/mg. This activity was significantly (P less than 0.05) higher in smokers (0.26 +/- 0.26) who had smoked until 1 week before surgery than in those who had stopped smoking for greater than 7 days (0.11 +/- 0.11). A positive linear correlation between DNA adduct levels and AHH activity (r = 0.69; P less than 0.001; n = 19) was found in smokers. This relationship could explain why AHH inducibility appears to be a crude marker for lung cancer risk in smokers.

Topics: Adult; Aged; Aryl Hydrocarbon Hydroxylases; DNA; Female; Humans; Lung; Lung Neoplasms; Male; Middle Aged; Phosphorus Radioisotopes; Smoking

In an attempt to probe for polycyclic aromatic hydrocarbon (PAH)-DNA adducts in human subjects resulting from smoking (or other chronic environmental exposure), lung tissue and lung tumours were obtained from patients hospitalized for lung cancer. DNA was isolated from the tissue samples and examined both in an ELISA using a polyclonal antibody against (+/-)trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10- tetrahydrobenzo[a]pyrene (BPDE)-DNA as well as by the nuclease P1-mediated modification of the 32P-post-labelling technique. The ELISA results showed BPDE-DNA antigenicity in lung DNA from 6 out of 21 patients, and adduct levels ranged from 2 to 134 adducts per 10(8) nucleotides. For all 21 patients, the autoradiographs of chromatograms of 32P-postlabelled digests of DNA from non-tumorous lung tissue showed a strong diagonal radioactive zone (DRZ). This DRZ was generally absent in tumorous tissue. DNA samples that were positive in the ELISA contained a dominant spot within the DRZ that co-chromatographed with the major BPDE-DNA adduct (BPDE-dG). The quantities of the BPDE-dG spots ranged from 2.1 to 42 adducts in 10(9) nucleotides. These values were lower than the levels found in the ELISA but correlated well with the ELISA results (Kendall W = 0.97; P = 0.00). The levels of the DRZ adducts ranged from 1.9 to 34 adducts in 10(8) nucleotides. Correlations between smoking and DNA adduct levels were poor because of the small number of current smokers (n = 13). However, smokers of filter cigarettes had significantly lower DNA adduct levels compared with smokers of cigarettes without a filter (P = 0.02 by Fischer's exact test).

Topics: 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; Autoradiography; Dihydroxydihydrobenzopyrenes; DNA; DNA Adducts; DNA, Neoplasm; Enzyme-Linked Immunosorbent Assay; Humans; Lung; Lung Neoplasms; Phosphorus Radioisotopes; Polycyclic Compounds; Smoking

Topics: Animals; Bone Neoplasms; Dogs; Lung Neoplasms; Microspheres; Organophosphorus Compounds; Phosphorus Radioisotopes; Radioisotopes; Samarium

To assess the utility of adducts of deoxyribonucleic acid (DNA) as biomarkers of exposure to carcinogens in an industrial population, a pilot study of roofers occupationally exposed to polycyclic aromatic hydrocarbons was conducted. DNA isolated from white blood cells of roofers and nonoccupationally exposed comparison subjects matched for age, sex, and smoking status was analyzed for DNA adducts with the use of 32P-postlabeling methods. Occupational exposures to polycyclic aromatic hydrocarbons were assessed by personal air sampling and skin wipes. Ten of the 12 roofers, but only 2 of the 12 comparison subjects, had detectable levels of aromatic DNA adducts in the 32P-postlabeling assay. Among the roofers, the post-shift levels of polycyclic aromatic hydrocarbons in the skin wipes were correlated with the DNA adduct levels. These results suggest that 32P-postlabeling assay may be useful for monitoring internal exposures to complex mixtures of aromatic hydrocarbons in industrial populations.

Topics: Adult; Biomarkers, Tumor; Cohort Studies; DNA; Environmental Exposure; Epidemiologic Methods; Humans; Isotope Labeling; Leukocytes; Lung Neoplasms; Male; Middle Aged; Phosphorus Radioisotopes; Pilot Projects; Polycyclic Compounds; Skin Neoplasms

Radioactive phosphorus (P-32) was administered intraperitoneally to Wistar female rats at 2-week intervals. P-32 was administered at a total dose of 3 mCi (a single dose of 200 microCi, 15 times) to Group 1, 2.4 mCi (1 microCi/g body weight, 15 times) to Group 2, and 1.4 mCi (1 microCi/g, 10 times) to Group 3. Osteosarcoma was induced in 29 out of 80 rats (36%) in Group 1, 28 out of 40 (70%) in Group 2, and 31 out of 40 (78%) in Group 3. Bone tumor was predominant in the trunk (spine, ilium etc.) in Group 1 (86%), and in the extremities (femur, tibia etc.) in Group 2 (64%) and Group 3 (71%). Histological findings revealed neoplastic osteoid formation in all lesions. Osteoblastic type developed more in Group 1 than in Group 3, and fibroblastic type developed more in Group 3 than in Group 1. The rate of lung metastasis was significantly higher in Group 3 (94%) than in Group 1 (21%, p less than 0.01) or Group 2 (72%, p less than 0.05). This experimental method, especially that used for Group 3, appears to be useful for studying the basis of human osteosarcoma.

Topics: Animals; Body Weight; Female; Lung Neoplasms; Neoplasms, Radiation-Induced; Osteosarcoma; Phosphorus Radioisotopes; Rats; Rats, Inbred Strains; Sarcoma, Experimental

Photoincorporation of 8N3-[gamma-32P]-GTP into tissue and cell extracts was examined using gel electrophoresis and autoradiography. Decreased photoincorporation into a 45kD band was observed in extracts from mouse lung tumors as compared to normal mouse lung, and in extracts from lung tumor-derived cell lines when compared to isolated bronchiolar epithelial cells. Decreased 45kD photolabelling was also observed in extracts of S49 lymphoma cyc- cells (deficient in Gs alpha, a 45kD GTP binding protein of receptor-coupled adenylate cyclase) when compared to wild type S49 cells. This, and the observation that there was no cholera toxin-catalyzed ADP-ribosylation in the 45kD band of lung tumor extracts, suggests that the 45kD band contains Gs alpha.

Topics: Affinity Labels; Animals; Azides; Cell Line; Guanosine Triphosphate; Lung; Lung Neoplasms; Mice; Mice, Inbred A; Molecular Weight; Neoplasm Proteins; Phosphorus Radioisotopes; Subcellular Fractions

Chromic colloidal phosphate labeled with 32P, which has been proposed for the treatment of several articular diseases, was injected intra-articularly in the knee joint of adult Wistar rats. After a 270 days minimum latent period, tumors began to appear in the injected zone, to a 70% frequency. Ten lung metastases were detected. In five cases, squamous cell carcinomas were induced in the injected area. The relevance of a sound evaluation of the risk involved in treatments with radioactive isotopes, is discussed.

Topics: Animals; Carcinoma, Squamous Cell; Hindlimb; Injections, Intra-Articular; Joint Diseases; Joints; Lung Neoplasms; Male; Neoplasms, Experimental; Neoplasms, Radiation-Induced; Osteosarcoma; Phosphorus Radioisotopes; Rats; Rats, Inbred Strains

Topics: Bronchoscopy; Fiber Optic Technology; Humans; Lung Neoplasms; Phosphorus Radioisotopes

Topics: Bone Neoplasms; Humans; Iodine Radioisotopes; Lung Neoplasms; Phosphorus Radioisotopes; Radionuclide Imaging; Strontium Radioisotopes; Technetium; Thyroid Neoplasms

Topics: Adult; Bronchi; Bronchoscopy; Humans; Lung Neoplasms; Male; Middle Aged; Phosphorus Radioisotopes; Radionuclide Imaging; Tuberculosis, Pulmonary

Topics: Child, Preschool; Humans; Japan; Leukemia, Radiation-Induced; Lung Neoplasms; Neoplasms, Radiation-Induced; Nuclear Warfare; Phosphorus Radioisotopes; Radium; Skin Neoplasms; Thorium Dioxide; Thyroid Neoplasms

Topics: Adult; Bronchography; Diagnosis, Differential; Female; Humans; Lung Neoplasms; Male; Middle Aged; Phosphorus Radioisotopes; Tuberculosis, Pulmonary

Topics: Animals; Cholesterol; Chromatography, Thin Layer; Fatty Acids, Nonesterified; Glycerophosphates; Lipids; Lung; Lung Neoplasms; Mice; Neoplasms, Experimental; Phosphatidylcholines; Phosphatidylethanolamines; Phosphatidylinositols; Phospholipids; Phosphorus Radioisotopes; Sphingomyelins; Triglycerides

Topics: Administration, Oral; Bronchial Neoplasms; Humans; Lung Neoplasms; Lymphatic Metastasis; Phosphorus Radioisotopes; Pneumonectomy; Preoperative Care; Scintillation Counting; Time Factors

Topics: Chromium Radioisotopes; Hodgkin Disease; Humans; Isotope Labeling; Leukemia, Lymphoid; Leukocyte Count; Leukocytes; Lung Neoplasms; Methods; Phosphorus Radioisotopes; Time Factors

Topics: Adult; Aged; Bronchography; Cyclophosphamide; Humans; Lung Neoplasms; Middle Aged; Phosphorus Radioisotopes

Topics: Breast Neoplasms; Exudates and Transudates; Gold Radioisotopes; Humans; Lung Neoplasms; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Radioisotopes

Topics: Humans; Lung Neoplasms; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary

Topics: Carcinoma, Bronchogenic; Chromium; Humans; Lung Neoplasms; Mediastinum; Phosphates; Phosphorus; Phosphorus Radioisotopes; Pneumonectomy; Pulmonary Surgical Procedures

Topics: Combined Modality Therapy; Lung Neoplasms; Mechlorethamine; Neoplasms; Nitrogen Mustard Compounds; Phosphorus; Phosphorus Radioisotopes

Topics: Lung Neoplasms; Mechlorethamine; Neoplasms; Nitrogen Mustard Compounds; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary