Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of therapy with four commonly used immunosuppressants--azathioprine, prednisolone, cyclophosphamide, and cyclosporine, on (UVI)-induced skin carcinogenesis were studied in the albino hairless (HRA/Skh-1) mouse. Following 30 weeks' exposure to UVI (290-400 nm) alone, 87% of mice developed skin tumors; the mean incidence of tumors at that time was 2.4 per mouse; and the tumors were predominantly papillomas (72%), with the remainder being carcinomas (25%) and keratoacanthomas (3%). Mice received immunosuppressive drug therapy beginning shortly after the start of UVI and continuing for up to 28 weeks. All drugs were given at immunosuppressive levels and dosages were comparable on a body weight basis to those used in clinical transplantation. Prednisolone had no effect on UVI-induced tumor development. Cyclosporine caused a moderate reduction in the latent period for tumor induction. Azathioprine and cyclophosphamide had strong promoting effects; the latent period for tumor induction was shortened and the tumor yield per mouse was increased (4.3 and 5.7 tumors per mouse, respectively, at 30 weeks after the start of UVI). Azathioprine, but not cyclophosphamide, also induced a larger proportion of carcinomas (43% and 15%, respectively). The results suggest that for kidney transplant recipients treated with the standard immunosuppressive drug regimen of azathioprine/prednisone, the increased susceptibility of the sun-exposed skin of these patients to squamous cell carcinoma is likely to be contributed to by specific promotion by the azathioprine therapy of the carcinogenic effects of sunlight.
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PMID:Effects of immunosuppressive therapy on the induction of skin tumors by ultraviolet irradiation in hairless mice. 362 91

The effects of immunosuppressive drugs on epidermal cell mitotic activity and the proliferative response of epidermis following ultraviolet radiation (UVR) were tested. Hairless (Skh-hr 1) mice were treated with immunosuppressive drugs at equivalent clinical doses with or without concomitant UVR (290-400 nm). Epidermal parameters measured were mitotic index (Im), rate of entry into mitosis (Fm), flash labelling index (FLI), rate of entry into DNA synthesis (Fs) and DNA content (flow cytometric analysis). In non-irradiated skin, prednisolone therapy depressed both mitotic activity and DNA synthesis; azathioprine and cyclosporin A had no effect; cyclophosphamide therapy increased the Fm and FLI values. Following repeated doses of UVR, there were enhanced mitotic activity and DNA synthesis in epidermis. Prednisolone therapy moderately depressed both proliferative responses; cyclophosphamide enhanced mitotic activity; azathioprine and cyclosporin A had no effect on these responses. The significance of these findings in relation to potential for increased susceptibility of skin to UV-induced carcinogenesis is discussed.
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PMID:Effects of ultraviolet radiation and immunosuppressive therapy on mouse epidermal cell kinetics. 394 38