phosphorus-radioisotopes and Precancerous-Conditions

The covalent binding of xenobiotics to DNA is an important trigger of the multistage process that leads to carcinogenesis. 32P-postlabeling represents a highly sensitive method for biomonitoring exposure to genotoxic agents and for cancer risk assessment; it is capable of detecting less than one DNA adduct per human genome. Recent improvements to the technique have shown that the resistance of adducted DNA to enzyme digestion may lead to an overestimation of the number of different adducts present in a sample.

Topics: Animals; Base Sequence; Cell Division; Cell Transformation, Neoplastic; DNA Adducts; Genome, Human; Humans; Models, Genetic; Molecular Sequence Data; Mutagenesis; Neoplasms; Phosphorus Radioisotopes; Precancerous Conditions; Radioisotope Dilution Technique; Sensitivity and Specificity; Xenobiotics

Topics: Anemia; Anemia, Sideroblastic; Animals; Chromosome Aberrations; Chromosome Disorders; Female; Granulocytes; Hematologic Diseases; Humans; Japan; Leukemia; Leukemia, Erythroblastic, Acute; Leukemia, Myeloid, Acute; Male; Mice; Middle Aged; Nuclear Warfare; Phosphorus Radioisotopes; Polycythemia Vera; Precancerous Conditions; Radiation Injuries; Thrombocytopenia

Carcinogen-resistant inbred DRH rats developed from the Donryu strain showed a remarkably low incidence of liver tumors when they were fed diets containing hepatocarcinogens such as 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB). In this work, we examined various characteristics of male DRH and Donryu rats during 3'-Me-DAB administration for 8 weeks. 32P-Postlabeling analysis showed that essentially similar levels of DNA-adducts were generated by the metabolites of 3'-Me-DAB in the livers of these two strains of rats at several time points. However, both GADD45 (growth arrest and DNA damage-inducible) and O6-methylguanine methyltransferase (putatively DNA damage-inducible) mRNA levels were increased significantly in Donryu rat livers, but were increased to a lesser extent in DRH rats. [3H]Thymidine incorporation into hepatic DNA began to increase around 10 to 20 days after the start of 3'-Me-DAB administration in Donryu rats probably due to DNA repair, while no significant change occurred in DRH rats under the same conditions. Furthermore, inductions of heme oxygenase (due to degradation of heme-proteins) and hepatocyte growth factor (HGF; cell death and regeneration of hepatocytes) mRNAs were greater in Donryu rat livers than those of DRH, suggesting that the former were more sensitive to cytotoxic effects of 3'-Me-DAB than the latter. Another remarkable difference observed between these two strains was the significant induction of cytochrome P-450 2E1 mRNA in Donryu rat livers; this may contribute to the generation of reactive oxygen intermediates. Finally, increases of glutathione S-transferase (P-form) and gamma-glutamyltranspeptidase mRNAs as marker enzymes of preneoplastic changes of hepatocytes were clearly seen only in Donryu rat livers at 6 to 8 weeks after the start of 3'-Me-DAB administration. These results indicate that the different susceptibility to hepatocarcinogenesis between these two strains of rats may arise from events other than the DNA adduct formation.

Topics: Animals; Carcinogens; DNA Adducts; DNA Damage; Drug Resistance; Gene Expression; Gene Expression Regulation; Liver; Liver Neoplasms, Experimental; Male; Methyldimethylaminoazobenzene; Phosphorus Radioisotopes; Precancerous Conditions; Rats; Rats, Inbred Strains; RNA, Messenger; Sensitivity and Specificity

DNA was extracted from the gastric mucosa of 69 patients and analysed for the presence of DNA adducts by 32P-postlabelling. Adduct levels found in patients with histologically normal gastric mucosa were compared with levels found in patients displaying evidence of chronic atrophic gastritis or intestinal metaplasia, both of which may be considered pre-malignant conditions. Adduct patterns were the same for all patients, but the highest adduct levels were found in the latter two groups. Mean adduct levels were also higher in patients with abnormal gastric mucosa, but there was no statistically significant difference in adduct levels between the normal and pre-malignant groups (P > 0.05, Mann-Whitney U test). Thus DNA adduct levels do not correlate with the presence of histological abnormalities in the stomach and are not useful as a marker of malignant potential.

Topics: Adult; Aged; Aged, 80 and over; DNA; DNA Damage; Female; Gastric Mucosa; Humans; Male; Middle Aged; Phosphorus Radioisotopes; Precancerous Conditions; Stomach Neoplasms

Topics: Adult; Aged; Biopsy, Needle; False Negative Reactions; Female; Humans; Hysterosalpingography; Middle Aged; Phosphorus Radioisotopes; Precancerous Conditions; Ultrasonography; Uterine Neoplasms

Topics: Cytodiagnosis; Female; Humans; Intraoperative Care; Ovarian Cysts; Ovarian Neoplasms; Ovary; Phosphorus Radioisotopes; Precancerous Conditions; Radionuclide Imaging

Exfoliated mucosal cells were collected from the oral cavity of three groups at high risk for oral cancer: Indian betel nut chewers, Filipino inverted smokers (burning end of cigar in mouth) and Indian Khaini tobacco chewers. DNA was extracted from these samples, as well as from samples of exfoliated cells of Canadian non-smoking controls. DNA was analyzed for the presence of aromatic DNA adducts using 32P-postlabelling analysis. Five chromatographically distinct adducts were found in samples from both the high risk groups and the nonsmoking controls. Individual adducts were detectable in approximately 30-95% of samples, depending on the adduct and population group. Estimated levels of specific adducts ranged from non-detectable (prevalence relative to normal nucleotides less than 1 X 10(-9)) to occasionally greater than 1 X 10(-7). No adducts were found in high risk groups which did not also appear in control subjects.

Topics: Adenosine Triphosphate; Adult; Affinity Labels; Areca; Chromatography, High Pressure Liquid; Chromatography, Thin Layer; DNA; Female; Humans; Male; Middle Aged; Mouth Mucosa; Mouth Neoplasms; Phosphorus Radioisotopes; Plants, Medicinal; Plants, Toxic; Precancerous Conditions; Risk; Smoking; Tobacco, Smokeless

Topics: Adnexa Uteri; Female; Humans; Ovarian Neoplasms; Phosphorus Radioisotopes; Precancerous Conditions; Radionuclide Imaging; Uterine Neoplasms; Uterus

Topics: Adolescent; Adult; Aged; Colposcopy; Cytodiagnosis; Female; Humans; Middle Aged; Phosphorus Radioisotopes; Precancerous Conditions; Sex Chromatin; Uterine Cervical Neoplasms

In 21 patients with a variety of skin tumors (squamous cell carcinomas, malignant melanomas, basal cell epitheliomas and mycosis fungoides) or pre-cancerous lesions (Bowen's disease, actinic keratosis, junctional nevus cell nevus) the radioactive phosphorus uptake test demonstrates a significantly increased concentration of P32 in those tumors. There were no false negative tests. The possibility of differentiation of malignant melanoma from benign nevus cell nevus and the early recognition of cutaneous metastases is described. Furthermore recurrence of previously irradiated or excised basal cell epitheliomas can be detected without a biopsy. No hematological side-effects were observed.

Topics: Aged; Bowen's Disease; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Diagnosis, Differential; False Negative Reactions; Female; Humans; Keratosis; Male; Melanoma; Middle Aged; Mycosis Fungoides; Neoplasm Metastasis; Neoplasm Recurrence, Local; Nevus, Pigmented; Phosphorus; Phosphorus Radioisotopes; Precancerous Conditions; Radionuclide Imaging; Skin Neoplasms

Topics: Adult; Ambulatory Care; Endometrium; Female; Humans; Middle Aged; Phosphorus Radioisotopes; Precancerous Conditions; Radionuclide Imaging; Uterine Neoplasms

Topics: Adult; Aged; DNA; Female; Humans; Middle Aged; Phosphorus Radioisotopes; Precancerous Conditions; Radionuclide Imaging; RNA; Uterine Neoplasms; Vaginal Smears

Topics: Adenosine Triphosphate; Animals; Cell Nucleus; Liver; Male; Methane; p-Dimethylaminoazobenzene; Phosphoproteins; Phosphorus Radioisotopes; Precancerous Conditions; Rats; Stimulation, Chemical; Time Factors

Topics: Humans; Phosphorus; Phosphorus Radioisotopes; Precancerous Conditions; Skin; Skin Neoplasms