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.
D000998:Antiviral Agents / Q000633:toxicity; D002478:Cells, Cultured; D003434:Crossing Over, Genetic / Q000187:drug effects*; D003857:Deoxyuridine / Q000031:analogs & derivatives* / Q000633:toxicity; D005260:Female; D005333:Fetus; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D008168:Lung / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D009152:Mutagenicity Tests; D009153:Mutagens; D011247:Pregnancy; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D013329:Structure-Activity Relationship
D000998:Antiviral Agents; D009153:Mutagens; D003857:Deoxyuridine