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ENHANCEMENT OF UV‐INDUCED SKIN CARCINOGENESIS BY AZATHIOPRINE: ROLE OF PHOTOCHEMICAL SENSITISATION
Author(s) -
KELLY GRAHAM E.,
MEIKLE WILLIAM D.,
MOORE DOUGLAS E.
Publication year - 1989
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/j.1751-1097.1989.tb04078.x
Subject(s) - phototoxicity , chlorpromazine , hairless , azathioprine , chemistry , metronidazole , carcinogenesis , pharmacology , dermatology , medicine , antibiotics , pathology , biochemistry , in vitro , gene , disease
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.