SCEs are induced by replication of BrdU-substituted DNA templates, but not by incorporation of BrdU into nascent DNA.
After 3 rounds of DNA replication in the presence of BrdU, third-division metaphase cells can be scored for the frequencies of SCEs that occurred during cycles 1 and 2, and also for the frequency of SCE during cycle 3. This procedure was used to resolve the issue of SCE induction by replication of BrdU-substituted DNA templates versus induction by BrdU incorporation into nascent DNA. It was observed that third-cycle SCE frequencies in CHO are dependent upon the amount of BrdU that was present during cycles 1 and 2 and are independent of the BrdU concentration during the third cycle. It is therefore BrdU serving as a template, rather than BrdU being incorporated, that initiates the SCE event. A model is proposed that produces reasonable fits to the observed data. It also predicts a true background or spontaneous SCE frequency of 3 per cell per cycle as previously reported by Heartlein et al. (Mutation Res., 107 (1983) (103-109). The predicted single twin ratio is higher than that reported by Wolff and Perry (Exp. Cell Res., 93 (1975) 23-30), and possible explanations for this discrepancy are discussed.
D000818:Animals; D001973:Bromodeoxyuridine / Q000494:pharmacology*; D002453:Cell Cycle; D002460:Cell Line; D006224:Cricetinae; D003434:Crossing Over, Genetic / Q000187:drug effects*; D004261:DNA Replication / Q000187:drug effects*; D008954:Models, Biological; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D013698:Templates, Genetic
D001973:Bromodeoxyuridine