ENHANCEMENT OF UV-INDUCED SKIN CARCINOGENESIS BY AZATHIOPRINE: ROLE OF PHOTOCHEMICAL SENSITISATION |
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| Authors: | GRAHAM E KELLY WILLIAM D MEIKLE DOUGLAS E MOORE |
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| Institution: | Departments of Surgery, The University of Sydney, N.S.W. 2006, Australia;Departments of Pharmacy, The University of Sydney, N.S.W. 2006, Australia |
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| Abstract: | Abstract 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. |
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