Effect of immunosuppressive agents and sunscreens on UV carcinogenesis in the hairless mouse.
The effect of two immunosuppressive agents, azathioprine and cyclophosphamide, with and without UVB sunscreen protection on UV-induced skin carcinogenesis was studied in the albino hairless mouse. In a daily treatment regime spanning 9 weeks, groups of mice were immunosuppressed with either drug, and were exposed to minimally erythemal doses of a light source simulating the UV portion of the solar spectrum. The accumulated UV exposure alone induced skin tumours in 77% of mice. Azathioprine, but not cyclophosphamide, significantly enhanced the incidence of UV tumorigenesis. Photoprotection by topical application of one of two commonly used UVB sunscreens, 2-ethyl-hexyl-p-methoxycinnamate (2-EHMC) or octyl-N-dimethyl-p-aminobenzoate (o-PABA), reduced the UV tumour incidence to zero in immunologically normal mice and to 8-15% in immunosuppressed mice. Unexpressed latent tumour initiations were revealed in all sunscreen-protected groups by the subsequent application of a tumour promoter, croton oil. In immunologically normal mice 2-EHMC had allowed initiations in 39% of UV-irradiated mice, and o-PABA in 16.5%. However, in UV-irradiated mice immunosuppressed with azathioprine there had been initiations in 78% of mice protected with 2-EHMC and 65% of mice protected with o-PABA. Photoprotected mice immunosuppressed with cyclophosphamide did not show the same increase in UV-initiations (22% with 2-EHMC, 23% with o-PABA). These results provide evidence that azathioprine increases the susceptibility of the skin to UV carcinogenesis. However, UVB sunscreens afford effective protection from overt tumour expression in the absence of a tumour promoter.
D010129:4-Aminobenzoic Acid / Q000494:pharmacology; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D001379:Azathioprine / Q000494:pharmacology*; D002278:Carcinoma in Situ / Q000209:etiology / Q000517:prevention & control; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000517:prevention & control; D002934:Cinnamates / Q000494:pharmacology; D003436:Croton Oil / Q000494:pharmacology; D003520:Cyclophosphamide / Q000494:pharmacology*; D005260:Female; D007111:Immunity, Cellular / Q000187:drug effects; D007636:Keratoacanthoma / Q000517:prevention & control; D051379:Mice; D008812:Mice, Hairless; D010212:Papilloma / Q000209:etiology / Q000517:prevention & control; D012878:Skin Neoplasms / Q000209:etiology / Q000517:prevention & control*; D013473:Sunscreening Agents / Q000494:pharmacology*; D014466:Ultraviolet Rays; D062366:para-Aminobenzoates
D002934:Cinnamates; D013473:Sunscreening Agents; D062366:para-Aminobenzoates; C015402:octyl dimethyl 4-aminobenzoic acid; C118580:octylmethoxycinnamate; D003436:Croton Oil; D003520:Cyclophosphamide; D001379:Azathioprine; D010129:4-Aminobenzoic Acid