Spontaneous and mitomycin-C induced sister-chromatid exchanges. Comparison of in vivo and in vitro systems.
Frequencies of sister-chromatid exchanges (SCE) were measured in vitro in mouse fibroblasts and in vivo in mouse bone-marrow cells. SCE levels in these cell systems were measured in response to varying concentrations of bromode-oxyuridine (BrdU) and mitomycin-C (MMC). Although BrdU was found to induce SCE in both cellular systems, baseline SCE levels were 2- to 3-fold higher in vitro than in vivo. SCE induction was found to be a linear function of MMC concentration in vivo and in vitro; however the slope of the vivo curve was 5-fold higher. The interaction of BrdU substituted DNA and MMC was examined by administering a fixed dose of MMC with increasing concentrations of BrdU. The induced SCE frequencies appeared to be additive. In addition to measuring drug-induced SCE, the BrdU differential staining technique allows concomitant measurement of the inhibition of cellular replication by the test drugs.
D000818:Animals; D001853:Bone Marrow / Q000648:ultrastructure; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D002875:Chromosomes / Q000187:drug effects*; D003434:Crossing Over, Genetic; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian / Q000166:cytology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL / Q000235:genetics; D008937:Mitomycins / Q000494:pharmacology*
D008937:Mitomycins; D001973:Bromodeoxyuridine