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The effects of the immunosuppressive drugs azathioprine, prednisolone and cyclosporin A, and UV irradiation on scheduled DNA synthesis, representing mitotic activity, and unscheduled DNA synthesis, representing DNA repair activity, in the skin of hairless mice were determined autoradiographically following intradermal administration of [3H]-thymidine. Azathioprine and prednisolone, and, to a lesser extent, cyclosporin A, were found to impair normal repair of UVR-induced DNA lesions in epidermal keratinocytes. Prednisolone, but not the other two drugs, further suppressed the normal delayed mitotic response in the skin following UVR. The depressive effects of these drugs, particularly the combined azathioprine/prednisolone regime, on scheduled and unscheduled DNA synthesis are considered likely to predispose skin to mutagenic and carcinogenic processes.

The phototoxicity of various drugs (chlorpromazine (CPZ), metronidazole (MET), 8‐methoxypsoralen (8‐MOP), azathioprine (AZA) and the azathioprine metabolites, 6‐mercaptopurine (6‐MP), methylnitrothio‐imidazole (MNTI), methylnitroimidazole (MNI)) was determined in hairless (Skh‐hrl) mice exposed to a light source with broad emission (290–700 nm). Chlorpromazine, MET, 8‐MOP, AZA, MNI and 6‐MP were phototoxic, as determined by the oedematous response of skin, at doses comparable to those used clinically. The effects of long‐term drug therapy and UV radiation on skin carcinogenesis were then determined. Chlorpromazine and MET, and to a lesser extent AZA, MNTI and 6‐MP, enhanced photocarcinogen‐esis. In each case, both the tumour yield and the proportion of malignant:benign skin tumours were increased. The results of this study imply that prolonged treatment of mice with low‐level phototoxins predisposes to photocarcinogenesis.

Oral retinoid therapy has been considered for the prevention of skin carcinogenesis in humans, although animal studies have failed to provide any evidence of a protective effect of these drugs in the one-step photocarcinogenic system. In this study, oral therapy with vitamin A or a synthetic analogue, etretinate, was tested for ability to protect hairless mice (Skh-hr1) from the development of skin tumours following exposure to broad-band light (280-700 nm) for 25 weeks. Retinoids were given by gavage 3 times weekly either at low dosage (2000 IU vitamin A or 4 mg etretinate per kg body weight) or high dosage (10,000 IU vitamin A or 20 mg etretinate per kg body weight). None of the retinoid therapies compared to control mice (gavage vehicle only) modified skin tumour production in terms of time to onset of tumours, total tumour yield, or the types of tumours produced.

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