Induction of sister-chromatid exchange by 5-substituted 2'-deoxyuridines.

Several 5-substituted 2'-deoxyuridine (dUrd) analogues, known for their anti-viral or anti-tumour potentials, were evaluated for their ability to induce sister-chromatid exchange (SCE) in human fibroblasts and lymphocytes. While the selective anti-herpes agents (E)-5-(2-bromovinyl)-dUrd, (E)-5-(2-chlorovinyl)-dUrd, (E)-5-(2-iodovinyl)-dUrd, (E)-5-(3,3,3-trifluoro-1-propenyl)-dUrd and (E)-5-(1-propenyl)-dUrd did not induce SCE unless their concentration was about 1000-5000-fold greater than that required to inhibit herpes-virus replication, several other dUrd analogues such as 5-vinyl-dUrd, 5-ethynyl-dUrd, 5-formyl-dUrd, 5-hydroxymethyl-dUrd and 5-trifluoromethyl-dUrd induced SCE at a concentration closely corresponding to those required to inhibit either virus replication or tumour-cell growth. Only 2 compounds, 5-fluoro-dUrd and 5-nitro-dUrd (5'-monophosphate), inhibited tumour-cell growth at a concentration well below that required for increased SCE induction. The ability of a given dUrd analogue to induce SCE may be related to its incorporation into DNA or, alternatively, may depend on an interaction with 5-bromo-dUrd, which is included in the tests to visualize SCE and which in itself produces SCE.

Citation

J J Cassiman, E de Clercq, H van den Berghe. Induction of sister-chromatid exchange by 5-substituted 2'-deoxyuridines. Mutation research. 1983 May-Jun;117(3-4):317-27

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PMID: 6855788

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