Induction of sister-chromatid exchanges (SCEs) by thymidine and the potentiation of mutagen-induced SCEs in Chinese hamster ovary cells.
The effect of nucleosides, a group of naturally occurring cell constituents, on the frequency of sister-chromatid exchange (SCE) in Chinese hamster ovary (CHO) cells has been studied. Addition of thymidine (TdR) to the culture medium causes a dose-dependent increase and at 100 microM concentration, the SCE frequency is approximately doubled. This effect is totally reversed by 200 microM deoxycytidine (dCdR) suggesting that deoxycytidine starvation is responsible for this enhancing effect. Neither dCdR by itself nor deoxyadenosine (dAdR) or deoxyguanosine (dGdR) up to 300 microM concentrations had any effect on the incidence of SCE. The frequency of SCE induced by 10(-7) M N-methyl-N-nitro-nitrosoguanine (MNNG) is increased 2-fold by the addition of 100 microM TdR and this effect is also cancelled by 200 microM dCdR. These results point to the importance of the balance in DNA-precursor pools for normal DNA synthesis, infidelity of replication and errors in the replication of alkylated DNA increasing when the precursor pools become unbalanced.
D000818:Animals; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D003434:Crossing Over, Genetic / Q000187:drug effects*; D003841:Deoxycytidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology*; D010053:Ovary; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D013936:Thymidine / Q000494:pharmacology*
D003841:Deoxycytidine; D008769:Methylnitronitrosoguanidine; D013936:Thymidine