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Mutagenic and antimutagenic effects of 5-substituted 2'-deoxyuridines depending on the nature of the 5-substituent

: Clerq, E. de; Boldt, J.; Marquardt, H.; Schäfer, A.; Westendorf, J.

Arzneimittel-Forschung 38 (1988), Nr.12, S.1820-1824
ISSN: 0004-4172
Fraunhofer ITA ( ITEM) ()
antimutagenic effect; genotoxicity; mutagenic effect; mutagenicity study; pyrimidine

Various 5-substituted pyrimidine 2'-deoxyribosides with antiherpes activity were investigated for their genotoxic activity. IDC, CEDC, CPDU, BVDU, EDU, DU and DT were non mutagenic in Salmonella typh. as well as in V79 Chinese hamster cells. IDU was moderately mutagenic and CEDU was highly mutagenic in V79 cells. Neither IDU nor CEDU were mutagenic in the bacterial assay. None of the compounds induced unscheduled DNA synthesis in primary rat hepatocytes. In addition, antimutagenic effects of 2'-deoxyuridines were discovered: in V79 cells, BVDU, EDU, DU and DT prevented the mutagenicity induced by CEDU. In these cells EDU also inhibited the mutagenicity induced by MNNG, DMBA or UV-light. The compounds were inacitve at inducing differentiation in hematopoetic cells. The significance of these data, particularly with regard to the use of 5-substituted 2'-deoxyuridines in anti-herpes therapy, is discussed.