Cell-cycle dependency of BUdR-induced mutation for six genetic markers in cultured mammalian cells.
Synchronized mouse L5178Y cells were treated with BUdR during each one of four sequential periods of the cell cycle (M-G1, early S, middle S and late S-G2). Among the 6 markers examined, asparagine independence (Asn+), 6-thioguanine resistance (TGr) and excess thymidine resistance (TdRr) showed maximal induction of mutation rates in the early S period, methotrexate resistance (MTXr) gave maximal induction during the middle S period, and two other markers [arabinosylcytosine resistance (Ara-Cr) and ouabain resistance (Ouar)] showed little mutation induction in any period under the experimental conditions. These results suggest that (i) genes responsible for Asn+, TGr and TdRr activity may be replicated in the early S period and the gene for MTXr activity replicated in the middle S period, and (ii) the mechanisms of mutation induction for the Ouar and Ara-Cr markers may be essentially different from those for the Asn+, TGr, TdRr and MTXr markers.
D000818:Animals; D001216:Asparagine / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000494:pharmacology*; D002453:Cell Cycle; D003561:Cytarabine / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D004351:Drug Resistance; D005796:Genes / Q000187:drug effects*; D007739:L Cells; D008727:Methotrexate / Q000494:pharmacology; D051379:Mice; D009154:Mutation; D010042:Ouabain / Q000494:pharmacology; D013866:Thioguanine / Q000494:pharmacology; D013936:Thymidine / Q000494:pharmacology
D003561:Cytarabine; D010042:Ouabain; D001216:Asparagine; D004247:DNA; D013866:Thioguanine; D001973:Bromodeoxyuridine; D013936:Thymidine; D008727:Methotrexate