phosphorus-radioisotopes and Skin-Neoplasms

We have developed a 32P-postlabelling method for quantifying ultraviolet irradiation (UV)-induced cyclobutane dimers and 6-4 photoproducts in human skin in situ. We review the application of the method in studies with human volunteers, demonstrating dose-response relationships over a wide range of administered doses, repair kinetics of UV-damaged DNA among healthy individuals and melanoma patients, and modulation by sunscreens, tan and constitutive pigmentation of damage induction. A notable finding is the wide interindividual variation in DNA damage immediately after irradiation and in its repair. Moreover, the protective effects of sunscreens against erythema and DNA damage also show wide interindividual variation. These results cannot be explained by variation in the experimental methods used. The worst-case scenario is that the differences between individuals are multiplicative, resulting in 1000-fold differences in sensitivity in the population, which would be likely to translate into differences in risk of skin cancer.

Topics: Biomarkers, Tumor; Chromatography, High Pressure Liquid; DNA Adducts; DNA Damage; Humans; Phosphorus Radioisotopes; Skin; Skin Neoplasms; Ultraviolet Rays

Topics: Animals; Cell Survival; Cells, Cultured; Conjunctiva; Dose-Response Relationship, Radiation; Eye Neoplasms; Fast Neutrons; Humans; Hyperbaric Oxygenation; Lentigo; Melanoma; Melanosis; Neoplasm Metastasis; Neoplasms, Experimental; Palliative Care; Phosphorus Radioisotopes; Radiation Effects; Radiotherapy Dosage; Skin Neoplasms

The PVSG was organized in 1967 to establish effective diagnostic criteria for polycythemia vera, to study the natural history of the disease and to define the optimal treatment. Although polycythemia vera and the other myeloproliferative diseases are relatively uncommon, the PVSG was able to accumulate well over 1,000 patients with these various disorders and to study them according to a total of 15 different protocols. PVSG-01, a long-term randomized controlled study of phlebotomy alone compared with the myelosuppressive agents, 32P or chlorambucil supplemented by phlebotomy, continues to receive follow-up data on 93% of surviving patients 18 years after initiation of the study. During its lifetime, PVSG has developed a widely accepted and highly effective set of criteria for the specific diagnosis of polycythemia vera as well as useful criteria for the diagnosis of essential thrombocythemia. It has gathered an enormous volume of data on the natural history of the myeloproliferative diseases and in particular on the nature of the prevalent complications, such as thrombotic events and hematologic and nonhematologic malignancies. With respect to the final question, the optimal treatment for polycythemia vera, it is apparent that the expectation of a single optimal therapy that would apply to all patients at all ages and stages of the disease was naive. Nevertheless considerable progress has been made. Moreover, the group has defined more precisely than ever before the nature of the complications of the disease and the association of the risks of specific complications with specific forms of therapy. It thus has made it possible to pose the next series of therapeutic questions that must be addressed in this disorder with a greater degree of sophistication than was previously possible.

Topics: Acute Disease; Age Factors; Bloodletting; Chlorambucil; Combined Modality Therapy; False Positive Reactions; Follow-Up Studies; Gastrointestinal Neoplasms; Gout; Hematocrit; Humans; Hydroxyurea; Leukemia; Phosphorus Radioisotopes; Platelet Aggregation; Platelet Count; Polycythemia Vera; Prospective Studies; Pruritus; Skin Neoplasms; Thrombosis

Topics: Administration, Topical; Adolescent; Adult; Aged; Arm; Child; Clinical Trials as Topic; Female; Humans; Iodine Radioisotopes; Leg; Lymph Nodes; Lymphatic Metastasis; Lymphography; Male; Melanoma; Middle Aged; Organophosphorus Compounds; Phosphorus Radioisotopes; Prognosis; Radioisotopes; Radiotherapy Dosage; Skin Neoplasms

Topics: Animals; Brachytherapy; Female; Phosphorus Radioisotopes; Skin Neoplasms

The study goal was to clarify the therapeutic effect and the absorbed dose of radionuclide phosphorus-32 for skin hemangiomas and the consequent risk of side effects in these patients. Phosphorus-32 is an β emitter and is used for skin hemangioma treatment. In comparison with the few Gy per minute of the linear accelerators, the dose rate of phosphorus-32 for hemangiomas is much <1 Gy/hour; so, the latter is called low-dose-rate radiation. To achieve the therapeutic dose, continuous hours or days of radiation is necessary. For strawberry hemangiomas, the phosphorus-32 applicator was tightly placed on the lesion site for several hours until reaching therapeutic dose. The absorbed dose was estimated by radiochromic films. The absorbed dose of phosphorus-32 irradiation declined exponentially with a depth from 0 to 2.5 mm. Of the 316 patients with strawberry hemangiomas, the lesion disappeared completely within 3 months after one-time treatment in 259 cases (82%). For cavernous hemangiomas, 370KBq phosphorus-32 colloid was injected into the hemangioma each square centimeter, and the absorbed radiation was estimated by theoretical calculation. Forty-two of the 58 patients with cavernous hemangiomas (72%) had lesions that completely disappeared within 3 months after receiving one to six treatments. Thus, the phosphorus-32 for strawberry hemangiomas and the chromium phosphate-32 colloid for cavernous hemangiomas were clearly efficacious.

Topics: Adolescent; Adult; Chromium Compounds; Dose-Response Relationship, Radiation; Female; Hemangioma, Cavernous; Humans; Infant; Male; Phosphorus Radioisotopes; Prognosis; Radiotherapy Dosage; Skin Neoplasms; Young Adult

This article describes a method for the preparation of (32)P patch for the treatment of skin cancer. It is based on the surface modification of a Nafion film by treatment with ZrOCl(2) solution, impregnation of a predicted quantity of (32)P into the film, and its subsequent immobilization into a nonleachable matrix by lamination. The effect of variations of critical parameters on the incorporation of (32)P into the membrane, such as solution pH, contact time, reaction volume, inactive carrier concentration of the feed, reaction temperature, and so on, was investigated to arrive at the conditions resulting in optimum retention of (32)P activity. The morphology of the membrane was evaluated by scanning electron microscope and energy dispersive spectral analyses. Quality control tests were carried out to ensure nonleachability, uniform distribution of activity, and stability of the patches.

Topics: Administration, Cutaneous; Brachytherapy; Carcinoma, Basal Cell; Fluorocarbon Polymers; Membranes, Artificial; Microscopy, Electron, Scanning; Phosphorus Radioisotopes; Radiopharmaceuticals; Skin Neoplasms; Zirconium

A facile, viable, "green" two-step, inexpensive technique was developed for the preparation of (32)P patch for the treatment of skin cancer. This technique consists of impregnation of H(3)(32)PO(4) solution into an inert solid carrier followed by immobilization into a nonleachable matrix by lamination. The morphology of the impregnated paper was evaluated by scanning electron microscope and energy-dispersive spectral analyses. Radioactive patches containing up to ∼37 MBq/cm(2) of (32)P could be prepared. Distribution of (32)P on sources was uniform and release of (32)P from the sealed source in water and saline was found to be well within the permissible levels of 185 Bq. Custom-shaped (32)P-patches after quality assurance were supplied to AIIMS, New Delhi, for clinical evaluation. (32)P-impregnated paper protected by a laminated film holds promise for treatment of superficial cancers.

Topics: Administration, Cutaneous; Animals; Autoradiography; Brachytherapy; Drug Delivery Systems; Humans; Mice; Mice, Inbred C57BL; Phosphorus Radioisotopes; Skin Neoplasms; Transdermal Patch

In recent years, specially designed patches containing beta emitters have been developed for contact brachytherapy of skin lesions. The aim of the present work was to evaluate the biological effects of the (32)P-patch on the skin of Sencar mice as a result of a brachytherapy treatment. For this purpose, a (32)P-patch was prepared with Chromic (32)P-phosphate and silicone and the classical model of two-stage skin carcinogenesis was reproduced in Sencar mice. Animals were divided in six groups. Four groups received the contact brachytherapy treatments using a scheme of a single session of 40 and 60Gy (SD40 and SD60) and a scheme of two sessions of 40 and 60Gy each (FD40 and FD60). The other two groups were used as controls of the single (CSD) and the fractionated (CFD) treatments. Radiation doses were estimated with equations derived from the MIRD DOSE scheme, and biologically effective doses (BED) were calculated according to equations derived from the linear-quadratic model. The endpoint to evaluate the treatments effects was tumor size after a follow-up period of 44 days. Finally, animals were sacrificed in order to get samples of all tumors for histological analysis and PCNA staining. Erythema, dermatitis and skin ulceration developed in almost all treated animals, but they gradually healed with regeneration of tissue during the follow-up period. Radiation effects on the skin of SD40, SD60, FD40 and FD60 showed a significant reduction of the tumor size with regard to controls, independently of the scheme and the radiation dose considered. PCNA staining scores of control groups were higher than for treated groups, independently of the scheme and the radiation dose considered. This radioactive (32)P-silicone-patch which is easy to prepare and use in the treatment of skin diseases, seems promising as a radioactive device for clinical use.

Topics: Administration, Cutaneous; Animals; Brachytherapy; Female; Mice; Mice, Inbred SENCAR; Phosphorus Radioisotopes; Proliferating Cell Nuclear Antigen; Radiotherapy Dosage; Skin; Skin Neoplasms

To evaluate the therapeutic effects of a (32)P-patch in the treatment of a murine melanoma.. Thirty male C57BL6 mice were divided into two groups: treated and control. Superficial tumors were induced in both groups by injecting B16F1 melanoma at about 10 cells/mouse subcutaneously. Tumors developed 10-15 days after transplantation and the (32)P-patch was applied on palpable tumors of the treated group. Tumor growth was followed up in both groups by measuring tumor size with a caliper. After the follow-up period, the animals were killed and tumor samples of the treated and control groups were collected for histological study by preparing paraffin sections stained with hematoxylin-eosin.. The (32)P-patch showed the absence of radioactivity leakage in vitro and the homogeneous distribution of the radionuclide. The skin surface at the application site of the (32)P-patch appeared hairless, and erythema developed, but reversed to normal after a few days in the treated group. Control of tumor growth was achieved in the treated group compared with the control group, although complete remission did not occur.. The (32)P-patch tested for the treatment of a murine melanoma model showed its efficacy, as tumor growth was retarded after application of the patch Nevertheless, adjustment of some therapeutic parameters and/or combining the patch with other treatment modalities may be necessary to achieve complete regression. The P-patch represents a powerful tool to individualize the treatment of melanoma.

Topics: Administration, Topical; Animals; Brachytherapy; Cell Line, Tumor; Dose Fractionation, Radiation; Male; Melanoma; Mice; Phosphorus Radioisotopes; Radioactive Tracers; Skin Neoplasms; Tumor Burden

The purpose of this study was to design and evaluate a 32P patch for brachytherapy of skin diseases. We employed Phosphoric-32P-acid and Chromic 32P-phosphate in combination with natural rubber or silicone to produce the patches. Stability studies in vitro to evaluate the leakage of radioactivity, autoradiographic studies to evaluate homogeneity and shielding, as well as therapeutic efficacy in an animal model of skin cancer of the selected 32P patch were performed. The 32P-silicone-patch demonstrated its safety for external application. Tumor growth was arrest and complete regressions of tumors were seen in some other cases with 40 Gy applied in a single-dose scheme. In conclusion, the 32P-silicone-patch is easy to prepare and use in the treatment of skin diseases.

Topics: Animals; Brachytherapy; Chromium Compounds; Drug Delivery Systems; Female; Histocytochemistry; Mice; Mice, Inbred SENCAR; Phosphates; Phosphoric Acids; Phosphorus Radioisotopes; Radiotherapy Planning, Computer-Assisted; Random Allocation; Rubber; Silicones; Skin Neoplasms

The objective of this study was to design and evaluate a 32P patch for the treatment of skin diseases.. The patch was prepared from chromic phosphate 32P and silicone. Bioelimination and biodistribution in healthy and treated animals, and the therapeutic efficacy of two treatment schemes (single dose and fractionated dose) in an animal model of skin cancer were studied.. Based on the bioelimination and biodistribution studies, no leakage of 32P from the patch was observed. The treated tumors reduced their mean diameter compared to controls. The single-dose therapeutic scheme showed a higher number of complete and partial remissions compared to the fractionated scheme. These results were confirmed by histopathological analysis of the samples.. The 32P patch was designed and produced according to specifications for the treatment of superficial lesions of the skin. Although the 32P patch is an open source, it behaves like a sealed one for use in brachytherapy treatments.

Topics: Administration, Cutaneous; Animals; Brachytherapy; Disease Models, Animal; Dose Fractionation, Radiation; Dose-Response Relationship, Radiation; Female; Metabolic Clearance Rate; Mice; Phosphorus Radioisotopes; Skin Neoplasms; Tissue Distribution; Treatment Outcome

Radioactive bandages incorporating 32P, a high-energy beta- emitter, were prepared with an aim to have a radiation source that can be used for the treatment of superficial tumors. 32P-Chromic phosphate particles were prepared and filtered through Millipore filters. Filter incorporating 32P activity was immobilized between nitrocellulose membranes and placed on an adhesive bandage. There was no leakage of radioactivity from the bandage when tested in saline. Efficacy of the radioactive bandage for treatment of superficial tumors was tested in melanoma-bearing C57BL/6 mice. A single dose of treatment with 74 MBq 32P bandage resulted in tumor growth delay, whereas multiple dose treatment with 74 MBq 32P bandage at twice-weekly intervals resulted in complete tumor regression when treatment was started, when the tumor was merely palpable. Histology sections from the treated animals showed absence of tumor.

Topics: Administration, Topical; Animals; Bandages; Equipment Design; Melanoma; Melanoma, Experimental; Mice; Mice, Inbred C57BL; Neoplasm Transplantation; Phosphorus Radioisotopes; Radiometry; Skin Neoplasms; Time Factors

The genotoxicity of extractable organic matter (EOM) from airborne particles in Shanghai has been determined using short-term bioassays. EOM samples were investigated using cell morphological transformation and two-stage model of mouse skin tumorigenicity assays to detect their carcinogenic activity. DNA adducts were detected using the 32P-postlabeling technique. The results showed that EOMs induced cell morphological transformation and played a role in tumor-initiating carcinogenesis. The EOMs of airborne particles from different districts of Shanghai had similar carcinogenic activity except the result of sample E (at downtown of Shanghai) was relatively high. The polycyclic aromatic hydrocarbon (PAH) fraction makes a major contribution to carcinogenic activity according to the results of cell morphological transformation assay. DNA adducts were also detected in skin, liver, and kidney of mouse after treatment with EOMs. It is suggested that the urban airborne particles in Shanghai, which show carcinogenic potential and genotoxic activity in our bioassays, may be responsible for the increased incidence of lung cancer in Shanghai in last few years.

Topics: 3T3 Cells; Air Pollutants; Air Pollution; Animals; Biotransformation; Carcinogens; Cell Survival; China; Cricetinae; DNA Adducts; Female; Fibroblasts; Male; Mesocricetus; Mice; Mice, Inbred BALB C; Mutagenicity Tests; Mutagens; Neoplasms, Experimental; Occupational Exposure; Organic Chemicals; Phosphorus Radioisotopes; Polycyclic Compounds; Skin Neoplasms; Tetradecanoylphorbol Acetate

The accurate assessment of microsatellite loci on specific chromosome regions for loss of heterozygosity (LOH) is important to identify potential tumor suppressor gene locations and recently correlations to clinicopathology of tumors. Analysis of microsatellite markers usually requires performing polymerase chain reaction (PCR) with labeled primers. This often leads to spurious PCR products that make interpretations of specific PCR bands difficult. Assessment of LOH by radiolabeled PCR is not always easy to interperet when there are multiple bands present, multiple markers and specimens are being assessed, and in multiplex LOH PCR. We describe an approach to accurately verify PCR-based LOH in which labeled PCR primers are not needed to detect allele expression. Specificity is determined by using a digoxigenin-labeled oligonucleotide (CA)13 as an internal specific probe for hybridization. Because the majority of di-nucleotide microsatellite markers contain the sequence of (CA)n or (GT)n repeats, this (CA)n probe is highly versatile. Forty cutaneous melanoma biopsies from advanced stage patients were assessed using the oligonucleotide probe at five chromosome regions (1q, 6q, 9p, 10q, 11q). The LOH frequency in informative cases varied from 33% to 47% in which chromosome 6q was the highest followed closely by 11q. We observed a higher frequency of LOH in the 6q (47%) and 11q (41%) compared to previously reported studies using the probe technique. This new approach was also demonstrated to be efficient in multiplex-PCR to detect LOH in melanomas. Using the probe hybridization approach it was demonstrated that in advanced cutaneous melanomas LOH are quite frequently expressed on 5 different chromosome regions.

Topics: Digoxigenin; Dinucleotide Repeats; DNA Probes; DNA, Neoplasm; Humans; Loss of Heterozygosity; Melanoma; Microsatellite Repeats; Phosphorus Radioisotopes; Skin Neoplasms

Understanding the basis for individual susceptibility to skin cancer requires an understanding of the factors contributing to tumorigenesis. One such factor is the ability of the cell to repair DNA lesions induced following insult to the genome. Currently, research in this field is hampered by the lack of a suitably sensitive and specific method for the detection of DNA lesions. Developed previously 32P-HPLC in vitro analysis is applied in this study to measure UVB-induced dipyrimidine photolesions in human keratinocyte cultures. The high sensitivity of this method permitted the detection of individual cyclobutane pyrimidine dimers and 6-4 photoproducts in cells irradiated with UVB at doses below one minimal erythema dose. Using this technique one could detect approximately a 2-fold difference in a base sequence repair of photolesions. The rates of repair in the chromosomally unstable HaCaT keratinocyte cell line and in cultured primary human keratinocytes were compared. The presented data indicate the potential of the 32P-HPLC method for the study of DNA repair in cultured cells as well as for biomonitoring studies in humans.

Topics: Cells, Cultured; Chromatography, High Pressure Liquid; DNA Adducts; DNA Damage; DNA Repair; Erythema; Humans; Keratinocytes; Phosphorus Radioisotopes; Phosphorylation; Photochemistry; Pyrimidine Dimers; Skin Neoplasms; Ultraviolet Rays

The immune complex kinase assay is the most widely applied method to assess the catalytic activity of protein tyrosine kinases. It offers the advantage that the activity of a single selected enzyme can be determined, and that the enzyme activity can be normalized for the amount of enzyme in a parallel immunoblotting experiment. Here, we describe the use of the recently introduced isotope phosphorus-33 for the protein kinase assay. The lower energy of 33P, compared with the traditionally applied 32P, allows the simultaneous examination of the amount of enzyme with 125I-labeled antibodies. By analysing one and the same sample for both kinase activity and protein amount, the variation between parallel processed samples is avoided. Using this method, specific kinase activities can be calculated with high precision. The assay is particularly useful for the detection of cytokine and growth factor-induced activation of kinases, as changes in enzyme amounts by subcellular relocalization can be distinguished.

Topics: Carcinoma; Glioblastoma; Humans; Immunoblotting; Methods; Neoplasm Proteins; Phosphorus Radioisotopes; Phosphotyrosine; Precipitin Tests; Protein-Tyrosine Kinases; Sensitivity and Specificity; Skin Neoplasms; Tumor Cells, Cultured

Ultraviolet B (UVB) component of the sunlight is the major cause of nonmelanoma skin cancer (NMSC) in humans. UVB is absorbed directly by cellular DNA and produces lesions that may cause mutation(s) in target gene(s) ultimately leading to cancer. Early detection of these lesions, therefore, may help to identify individuals at a high risk to develop NMSC, and devise approaches for the prevention of this common malignancy. Employing mouse skin as a model, we applied a 32P postlabelling method to detect UVB-induced DNA lesions in the epidermis in nanomole quantities. Autoradiography maps showed that epidermal DNA from UVB exposed mice at 24 h contain up to five DNA lesions; the quantitation of these lesions showed that their formation increased in a UVB dose-dependent manner. Treatment of DNA samples with the bacteriophage DNA repair enzyme T4 endonuclease V confirmed that four of these lesions are pyrimidine dimers. While, some of these lesions were repaired 18 h after UVB irradiation, 30% of them persisted even 48 h post-irradiation. Application of a sunscreen containing ethylhexyl-p-methoxycinnamate or chemopreventive agent green tea polyphenols or silymarin to the skin of the mice prior to UVB exposure was found to prevent the formation of pyrimidine dimers.

Topics: Animals; DNA; Epidermis; Female; Guanosine Triphosphate; Mice; Mice, Hairless; Phosphorus Radioisotopes; Pyrimidine Dimers; Silymarin; Skin Neoplasms; Sunscreening Agents; Ultraviolet Rays

We have previously shown that the 180-kD bullous pemphigoid antigen (BPAII), which is a transmembrane collagenous protein of hemidesmosomes, is distributed at adhesion sites on glass coverslips on the basal membrane forming a concentric ring, or arch pattern, in a human squamous cell carcinoma cell line (DJM-1), when studied by immunofluorescence microscopy using monoclonal antibodies to BPA II. This concentric ring/arch pattern of "footsteps" of BPA II has been shown to be collapsed in association with a transient activation of protein kinase C by treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA). In the present study, therefore, the effects of TPA on the phosphorylation of BPA II was examined. DJM-1 cells, which were metabolically labelled with [32Pi], were lysed and the extracts were subjected to immunoprecipitation with anti-BPAII and anti-230 kDa bullous pemphigoid antigen (BPAI) monoclonal antibodies. The results showed that only BPA II, but not BPA I, was phosphorylated at serine residues before TPA treatment. After TPA treatment phosphorylation was prominently increased so as to generate a 190 kDa-phosphorylated peptide. This 190-kDa peptide was reacted with anti-BPA II monoclonal antibodies by immunoblotting, and it was not detected when cells were pretreated with a specific protein kinase C inhibitor (H7) before TPA treatment, suggesting that the 190 kDa peptide is phosphorylated BPAII with TPA. Prolonged treatment with TPA abolished both of 180- and 190-kDa BPA II from Triton X-100-soluble fractions. These findings suggest that the BPA II, but not BPA I, is a substrate of protein kinase C, and the generation of 190-kDa-phosphorylated BPA II has a key role in the TPA-induced collapse of the assembly of BPA II on the basal plasma membrane, probably, at hemidesmosomes.

Topics: Amino Acids; Animals; Antibodies, Monoclonal; Autoantigens; Autoradiography; Blotting, Western; Carcinoma, Squamous Cell; Carrier Proteins; Cattle; Cell Adhesion; Collagen; Collagen Type XVII; Cornea; Cytoskeletal Proteins; Desmosomes; Dystonin; Epithelial Cells; Epithelium; Humans; Nerve Tissue Proteins; Non-Fibrillar Collagens; Pemphigoid, Bullous; Phosphorus Radioisotopes; Phosphorylation; Precipitin Tests; Skin Neoplasms; Tetradecanoylphorbol Acetate; Tumor Cells, Cultured

In squamous cell carcinomas (SCCs), the tumor suppressor protein p53 is frequently overexpressed. The overexpression of p53 is often due to a mutation in the p53 gene; however, increased levels of p53 protein can be observed in the tumors without p53 gene mutations. In normal human keratinocytes, p53 is a multiconformational protein. The different conformations of p53 can be identified by their reactivity with epitope-specific, anti-p53 monoclonal antibodies. This study provides evidence that the different p53 conformations seen in human keratinocytes bind to distinct cellular proteins. Proteins that bind p53 in normal human keratinocytes were compared with p53-binding proteins from cells derived from SCC tumors by immunoprecipitation of [35S]methionine-labeled and 32P(i)-labeled cell lysates using a panel of anti-p53 monoclonal antibodies. In one tumor, the SCC cells contained a protein of Mr 30,000 bound to p53 that was not seen in normal human keratinocytes. Cells derived from a separate SCC did not have the Mr 30,000 protein but did contain two proteins of Mr 15,000 and Mr 16,000, which were not seen in normal human keratinocytes. The immunofluorescent staining pattern of cultured normal human keratinocytes, cells derived from two SCCs, as well as the original tumors from which the cells were derived, was also examined. The immunofluorescent staining of the cells derived from the tumors and the tumors themselves was different from that seen in normal cultured keratinocytes and normal epidermis. These studies suggest that there are alterations in the proteins that bind to p53 in SCCs.

Topics: Carcinoma, Squamous Cell; Carrier Proteins; Cells, Cultured; Electrophoresis, Polyacrylamide Gel; Fluorescent Antibody Technique; Humans; Infant, Newborn; Keratinocytes; Male; Methionine; Molecular Weight; Phosphates; Phosphorus Radioisotopes; Reference Values; Skin; Skin Neoplasms; Sulfur Radioisotopes; Tumor Suppressor Protein p53

Coal tar, a tumour initiator, and dithranol, a tumour promoter, are used in the treatment of psoriasis. Topical treatment of mice with pharmaceutical formulations of these two agents, at therapeutic doses, induced skin papillomas in a classical two-stage carcinogenesis protocol, while treatment with either agent alone did not. This finding has implications for the use of both agents in combination in the treatment of psoriasis.

Topics: Adenosine Triphosphate; Administration, Topical; Animals; Anthralin; Benzo(a)pyrene; Carcinogens; Coal Tar; DNA; DNA, Neoplasm; Female; Mice; Ointments; Phosphorus Radioisotopes; Psoriasis; Skin Neoplasms

The genotoxicities in vitro and in vivo of the mouse-skin carcinogen 7,12-dimethylbenz[a]anthracene (DMBA) have been compared with those of its weakly carcinogenic 4,5-sulphur analogue, 6,11-dimethylbenzo[b]naphtho-[2,3-d]thiophene (S-DMBA). The only datasets that correlated with the relative carcinogenicity of these agents to the skin were those conducted using topically exposed mouse skin. Thus, both chemicals induced lacZ- mutations in the skin of lacZ+ transgenic mice, and both produced DNA adducts on mouse-skin DNA as assessed using the 32P-postlabeling technique. In each case, DMBA gave a stronger response than did S-DMBA. In contrast to these responses, only DMBA was active in the mouse bone-marrow micronucleus assay and in the C3H10T1/2 in vitro cell transformation assay. Both chemicals were mutagenic to Salmonella and of approximately equal potency. The molecular geometry of DMBA and S-DMBA are compared, and divergent CASE predictions of activity in the Salmonella assay and skin-painting bioassay are discussed. The importance of conducting predictive genotoxicity assays in systems close to those in which carcinogenicity is to be assessed is emphasized by these data.

Topics: Aniline Compounds; Animals; Carcinogens; Lac Operon; Male; Mice; Mice, Inbred C3H; Mice, Inbred CBA; Mice, Transgenic; Molecular Structure; Mutagenicity Tests; Mutagens; Phosphorus Radioisotopes; Polycyclic Compounds; Skin; Skin Neoplasms; Thiophenes

The turnover of 32P-labeled phospholipids in HUT 102 lymphoblasts was determined after a 2 h interaction of lymphoblasts with 8-methoxypsoralen (8-MOP) (15 micrograms ml-1), longwave UV light (UVA) irradiation and PUVA (8-MOP and UVA). In parallel experiments, micellar suspensions of lyso-phosphatidylcholine (PtdC), dipalmitoyl-PtdC and dilinoleoyl-PtdC, treated in a similar manner, served for the correlative assessments of cellular lipid changes. The dark reaction, UVA irradiation and PUVA all depressed total phospholipid levels in HUT 102 cells, although only PUVA induced a statistically significant decline. Thin layer chromatography (TLC) analysis revealed that neither UVA nor 8-MOP alone triggered any significant changes in the cellular content of phosphatidylinositol (PtdI), phosphatidylinositol 4-monophosphate (PtdIP) and phosphatidylinositol 4,5-bisphosphate (PtdIP2), whereas the lyso-PtdC and PtdI content of lymphoblasts showed a two-fold increase after PUVA. The TLC analysis of lyso-PtdC and micelles of dipalmitoyl-PtdC did not reveal any detectable changes after the dark reaction with 8-MOP, UVA irradiation and PUVA. In contrast, the derivatives of dark and UVA mediated reactions of 8-MOP with dilinoleoyl-PtdC were detected by TLC. These results suggest that the formation of 8-MOP derivatives of cellular phospholipids effected by PUVA, modulates the turnover of phosphoinositides and the rate of cellular proliferation.

Topics: Cell Line; Chromatography, Thin Layer; Humans; Lymphoma, T-Cell; Methoxsalen; Phosphatidylcholines; Phosphatidylinositols; Phospholipids; Phosphorus Radioisotopes; Skin Neoplasms; Ultraviolet Rays

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

Garlic extract was proved to inhibit one of the earliest phenomena caused by 12-O-tetradecanoyl-phorbol-13-acetate (TPA), a tumor promoter, in vitro; i.e., the enhancement of phospholipid metabolism. And also the first stage of tumor promotion in two-stage mouse skin carcinogenesis in vivo was suppressed by the treatment with garlic extract. Thus, garlic extract seems to be effective to inhibit initial events caused by TPA type tumor promoters in vitro and in vivo.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Carcinogens; Female; Garlic; HeLa Cells; Mice; Mice, Inbred ICR; Phospholipids; Phosphorus Radioisotopes; Plant Extracts; Plants, Medicinal; Skin Neoplasms; Tetradecanoylphorbol Acetate

This study deals with the mechanism of the inhibitory effect exerted by the immunosuppressant ciclosporin (CsA) on phorbol-ester-induced inflammation, epidermal hyperplasia and tumor promotion in mouse skin in vivo. This effect coincides with an inhibition of the phosphorylation of a 100-kilodalton protein (p100) in epidermal cytosol in vitro, which has been identified as elongation factor 2 (EF-2) of protein biosynthesis. Phosphorylation of EF-2 is dependent on Ca2+ and calmodulin, and inhibition of EF-2 phosphorylation by CsA is due to an interaction of CsA with calmodulin. The EF-2 phosphorylation system has a metabolic half-life of 1.5 h probably due to a rather rapid turnover rate of the EF-2 kinase. Since CsA inhibits specifically 12-O-tetradecanoylphorbol-13-acetate (TAP)-stimulated but not basal protein synthesis in epidermis, it is proposed that Ca2+/calmodulin-dependent phosphorylation of EF-2 is involved in the induction of the hyperplastic response by TPA and that CsA suppresses TPA effects by inhibition of EF-2-phosphorylation and perhaps other calmodulin-dependent processes. The potential applicability of calmodulin inhibitors in the treatment of hyperproliferative skin diseases is discussed.

Topics: Animals; Calcium; Calmodulin; Cell Transformation, Neoplastic; Chromatography, DEAE-Cellulose; Cocarcinogenesis; Cycloheximide; Cyclosporins; Cytosol; Electrophoresis, Polyacrylamide Gel; Mice; Peptide Elongation Factor 2; Peptide Elongation Factors; Phosphorus Radioisotopes; Phosphorylation; Skin; Skin Neoplasms; Tetradecanoylphorbol Acetate

Glycyrrhetic acid suppressed tumor promoter-induced effects in vitro, such as stimulation of 32Pi-incorporation into phospholipids of cultured cells and down-regulation of the epidermal growth factor receptor. Glycyrrhetic acid inhibited the promoting activity of both 12-O-tetradecanoylphorbol-13-acetate (TPA) and teleocidin on skin tumor formation in mice initiated with 7,12-dimethylbenz[a]anthracene (DMBA). The percentage of tumor-bearing mice in the group treated with DMBA plus teleocidin was 88% at week 18, whereas that in the group treated with DMBA plus teleocidin and glycyrrhetic acid (10 mumol/painting) was 6%. Similarly, the percentage of tumor-bearing mice of the group treated with DMBA plus TPA was 97% at week 20, whereas that of the group treated with DMBA plus TPA and glycyrrhetic acid was 40%. Therefore, glycyrrhetic acid was proved to inhibit the activity of two different tumor promoters, teleocidin and TPA, in mouse skin.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; ErbB Receptors; Female; Glycyrrhetinic Acid; HeLa Cells; Lyngbya Toxins; Mice; Mice, Inbred ICR; Phorbols; Phospholipids; Phosphorus Radioisotopes; Quercetin; Receptors, Cell Surface; Skin Neoplasms; Sulfonamides; Tetradecanoylphorbol Acetate; Time Factors

Topics: Copper; Diagnosis, Differential; Diphosphates; Humans; Melanoma; Phosphorus Radioisotopes; Skin Neoplasms

A complex of new methods are proposed. They make it possible to improve the precision and informative value of the results of 32P diagnosis of pigmental skin tumors. The following methods are used: 1) fractional administration of the indicator to increase the level of 32P accumulation in melanomas; it made it possible to improve the differential-diagnostic capacity of the radiophosphorus test; 2) beta-radiometry of pathological and control skin zones with and without fine tissue equivalent filters to "contrast" tumors and to determine the average depth of their invasion to unchanged tissues; the use of this method made it possible to lessen the number of false-negative diagnoses and to get additional clinicodiagnostic information that can be useful in the planning of surgical and radiation treatment; 3) radiometry of skin zones in the spectrometric regimen with three different levels of the integral discrimination of beta-radiation impulses to determine the thickness and lower line of the layer of the abnormal accumulation of the indicator in the pathological skin zone; the use of this method makes it possible to detect incrusted melanomas.

Topics: Diagnosis, Differential; Humans; Mathematics; Melanoma; Methods; Neoplasm Invasiveness; Phosphorus Radioisotopes; Radionuclide Imaging; Skin; Skin Neoplasms; Tissue Distribution

The authors have determined the distribution of 32P in normal skin and in the case of certain skin tumours (basalioma and spinalioma). In both groups a lognormal distribution was found. It may be assumed that the enrichment is governed by similar distribution in the case of melanoma malignum.

Topics: Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Humans; Mathematics; Melanoma; Phosphorus Radioisotopes; Skin; Skin Neoplasms

Topics: Female; Humans; Immunity, Cellular; Injections, Intralymphatic; Male; Melanoma; Middle Aged; Phosphorus Radioisotopes; Radiotherapy; Skin Neoplasms

A complex examination by radio-isotope (32P) and thermographic methods was carried out in 252 patients, 122 patients underwent surgery. The complex diagnostic study established the following three groups: test-positive, test-negative and test-suspected patients. Application of the complex (radioisotope and thermographic) examination technique provides a more adequate visualization of tumor process and, therefore, a better opportunity for selection of correct treatment. The application of the thermographic method is recommended for screening for subjects at high risk of malignant disease of the skin.

Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Diagnosis, Differential; Female; Humans; Lymphatic Metastasis; Male; Melanoma; Middle Aged; Nevus, Pigmented; Phosphorus Radioisotopes; Pigmentation Disorders; Radionuclide Imaging; Skin Neoplasms; Thermography

Topics: Adult; Diagnosis, Differential; Female; Humans; Male; Melanoma; Middle Aged; Phosphorus Radioisotopes; Radionuclide Imaging; Skin Neoplasms

Topics: Adult; Diagnosis, Differential; Female; Humans; Male; Melanoma; Methods; Middle Aged; Nevus, Pigmented; Phosphorus Radioisotopes; Skin Neoplasms

Topics: Humans; Lymphatic Metastasis; Melanoma; Methods; Neoplasm Staging; Phosphorus Radioisotopes; Radionuclide Imaging; Skin Neoplasms

Topics: Diagnosis, Differential; Humans; Melanoma; Phosphorus Radioisotopes; Radionuclide Imaging; Skin Neoplasms

Topics: Female; Humans; Lymph Nodes; Lymphatic Metastasis; Male; Melanoma; Palliative Care; Phosphorus Radioisotopes; Prognosis; Skin Neoplasms; Time Factors

Endolymphatic isotope therapy had such promising early clinical results that the M.R.C. (Medical Research Council) U.K. set up a clinical trial in 1966. This was to compare the effect of endolymphatic isotope therapy with the results of standard methods in the treatment of lower limb malignant melanoma. The interim report had three groups for analysis: Standard Methods (S); Endolymphatic Satisfactory (ES); and Endolymphatic Unsatisfactory (EU). This third group was a subdivision, as a significant number of patients did not have the correct endolymphatic treatment. The five-year survival figures expressed as actuarial percentages were ES=78.8%; S=82.3%; and EU=57.3%. Lymph node recurrence showed a significant difference: ES=2.3%; EU=12%; and S=19%. The conclusions were that endolymphatic isotope therapy was justified in specialized centres where good results could be obtained. Further animal experiments using the VX2 tumour in rabbits indicated that BCG given intracutaneously or intravenously had no therapeutic effect, whereas when applied by intralymphatic injection BCG was successful in treating lymph node metastases. Nineteen patients with poor-prognosis malignant melanoma have received endolymphatic BCG. The clinical results are recorded in this paper and are sufficiently encouraging to warrant its continued use.

Topics: Animals; BCG Vaccine; Female; Humans; Injections, Intralymphatic; Iodine Radioisotopes; Lymphatic Metastasis; Male; Melanoma; Middle Aged; Neoplasms, Experimental; Phosphorus Radioisotopes; Rabbits; Skin Neoplasms

Topics: Diagnosis, Computer-Assisted; Elementary Particles; Humans; Mathematics; Phosphorus Radioisotopes; Radiometry; Radionuclide Imaging; Skin Neoplasms; Time Factors

Topics: Hemangioma; Humans; Infant; Phosphorus Radioisotopes; Radiotherapy Dosage; Skin Neoplasms; Yttrium Radioisotopes

Topics: Humans; Phosphorus Radioisotopes; Skin Neoplasms; Skin Pigmentation

In localized malignant melanoma, preoperative irradiation with fast electrons followed promptly by operation is recommended. With melanomas of the lower extremities additional endolymphatic radiotheraphy (32-P) is given. The present authors results with 139 patients are comparable with those presented by Edwards (London) and Ariel (New York). Cutaneous spread or lymph-node metastases should be excised widely and this should be followed by irradiation, fast electrons being preferable.

Topics: Electrons; Germany, West; Humans; Injections, Intralymphatic; Lymph Node Excision; Lymphatic Metastasis; Melanoma; Phosphorus Radioisotopes; Radiotherapy, High-Energy; Skin 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: Child, Preschool; Humans; Japan; Leukemia, Radiation-Induced; Lung Neoplasms; Neoplasms, Radiation-Induced; Nuclear Warfare; Phosphorus Radioisotopes; Radium; Skin Neoplasms; Thorium Dioxide; Thyroid Neoplasms

A case of malignant melanoma involving the regional lymphnodes was treated by endolymphatic isotope therapy. Because of the great diameter the radiation of some metastases was not completely sufficient. Fluorescent and living cells of malignant melanoma between damaged cells could be seen in the center of these metastases. Melanophages surrounded concentrically the central part of the metastases enclosing the melanoma cells. It is shown that in the search and identification for pigment producing melanoma cells the fluorescent histochemical method of Falck-Hillarp is superior to usual light microscopical methods. Beyond of this, the phenomenon of fluorescence in malignant melanoma cells probably is an indication for the vitality of these cells.

Topics: Aged; Humans; Iodine Radioisotopes; Lymph Nodes; Lymphatic Metastasis; Lymphography; Male; Melanoma; Microscopy, Fluorescence; Phosphorus Radioisotopes; Skin Neoplasms; Toes

Topics: Humans; Lymph Nodes; Lymphatic Metastasis; Melanoma; Palliative Care; Phosphorus Radioisotopes; Radiation Effects; Radiotherapy Dosage; Radiotherapy, High-Energy; Skin Neoplasms

Topics: Extremities; Humans; Injections, Intralymphatic; Iodized Oil; Melanoma; Pharmaceutical Vehicles; Phosphorus Radioisotopes; Skin Neoplasms

Topics: Humans; Melanoma; Phosphorus Radioisotopes; Skin Neoplasms

Topics: Adult; Female; Humans; Melanoma; Middle Aged; Phosphorus Radioisotopes; Skin Neoplasms

Topics: Aged; Eyelid Neoplasms; Female; Humans; Male; Middle Aged; Phosphorus Radioisotopes; Skin Neoplasms

Topics: Animals; Carcinoma; Iodine Radioisotopes; Iodized Oil; Lymph Nodes; Lymphatic Metastasis; Neoplasms, Experimental; Organ Size; Organophosphorus Compounds; Phosphorus Radioisotopes; Rabbits; Radioisotope Teletherapy; Radionuclide Imaging; Radiotherapy Dosage; Skin Neoplasms; Triolein

Topics: Adult; Female; Humans; Knee; Leg; Lymph Node Excision; Lymphatic Metastasis; Lymphography; Male; Melanoma; Middle Aged; Phosphorus Radioisotopes; Radionuclide Imaging; Skin Neoplasms

Topics: Gold Isotopes; Humans; Indium; Lymphatic Metastasis; Lymphography; Melanoma; Phosphorus Radioisotopes; Radionuclide Imaging; Skin Neoplasms

Topics: Early Diagnosis; Humans; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Skin; Skin Neoplasms

Topics: Hemangioma; Humans; Phosphorus; Phosphorus Radioisotopes; Radioactivity; Radioisotopes; Skin Neoplasms

Topics: Diagnosis, Differential; Eye Neoplasms; Humans; Nevus; Nevus, Epithelioid and Spindle Cell; Nevus, Pigmented; Phosphorus; Phosphorus Radioisotopes; Skin Neoplasms

Topics: Animals; Carcinoma, Squamous Cell; Fibrosarcoma; Mice; Neoplasms, Experimental; Phosphorus; Phosphorus Radioisotopes; Sarcoma, Experimental; Skin; Skin Neoplasms; Strontium; Strontium Radioisotopes

Topics: Humans; Phosphorus; Phosphorus Radioisotopes; Skin Neoplasms

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

Topics: Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Radioactivity; Skin Neoplasms

Topics: Humans; Melanoma; Melanoma, Cutaneous Malignant; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Skin Neoplasms

Topics: Humans; Melanoma; Melanoma, Cutaneous Malignant; Phosphorus; Phosphorus Radioisotopes; Skin Neoplasms

Topics: Diagnosis, Differential; Humans; Melanoma; Nevus; Nevus, Pigmented; Phosphorus; Phosphorus Radioisotopes; Skin Neoplasms

Topics: Phosphates; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Radioactivity; Skin Neoplasms; Suspensions

Topics: Hemangioma; Humans; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Radioactivity; Skin Neoplasms

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

Topics: Eye Neoplasms; Humans; Melanoma; Melanoma, Cutaneous Malignant; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Skin Neoplasms

Topics: Cobalt; Cobalt Radioisotopes; Gold Radioisotopes; Phosphorus; Phosphorus Radioisotopes; Radioisotopes; Skin Neoplasms; Strontium; Strontium Radioisotopes

Topics: Capillaries; Humans; Nevus; Nevus, Pigmented; Phosphorus; Phosphorus Radioisotopes; Skin Neoplasms

Topics: Humans; Melanoma; Nevus; Nevus, Pigmented; Phosphorus; Phosphorus Radioisotopes; Skin Neoplasms

Topics: Bone Neoplasms; Breast Neoplasms; Humans; Phosphorus; Phosphorus Radioisotopes; Skin Neoplasms

Topics: Humans; Phosphorus; Phosphorus Radioisotopes; Radioactivity; Skin Neoplasms