用免疫抑制药物和UVB-UVA照射处理的无毛小鼠表皮细胞中的定时和非定时DNA合成。

Scheduled and unscheduled DNA synthesis in epidermal cells of hairless mice treated with immunosuppressive drugs and UVB-UVA irradiation.

作者信息

Kelly G E, Meikle W, Sheil A G

机构信息

Department of Surgery, University of Sydney, NSW, Australia.

出版信息

Br J Dermatol. 1987 Oct;117(4):429-40. doi: 10.1111/j.1365-2133.1987.tb04922.x.

DOI:10.1111/j.1365-2133.1987.tb04922.x

PMID:3676092

Abstract

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.

摘要

在给无毛小鼠皮内注射[3H] - 胸腺嘧啶核苷后，通过放射自显影法测定免疫抑制药物硫唑嘌呤、泼尼松龙和环孢素A以及紫外线照射对代表有丝分裂活性的定时DNA合成和代表DNA修复活性的不定时DNA合成的影响。结果发现，硫唑嘌呤和泼尼松龙，以及程度较轻的环孢素A，会损害表皮角质形成细胞中紫外线辐射诱导的DNA损伤的正常修复。泼尼松龙，而非其他两种药物，会进一步抑制紫外线照射后皮肤中正常的延迟有丝分裂反应。这些药物，尤其是硫唑嘌呤/泼尼松龙联合用药方案，对定时和不定时DNA合成的抑制作用可能会使皮肤易发生致突变和致癌过程。