Mutagen-induced changes in cellular deoxycytidine triphosphate and thymidine triphosphate in Chinese hamster ovary cells.
Deoxynucleoside triphosphate concentrations in Chinese hamster ovary cell lines, CHO-K1 and Mut 8-16, were examined following exposure of cells to UV or dimethylsulfate. Marked decreases in dCTP were observed 2 hr after exposure to both mutagens. In contrast, dTTP concentrations increased with increased cell killing after exposure to UV but not after exposure to dimethylsulfate. Examination of DNA synthesis in permeabilized cells in the presence of excess concentrations of dNTP substrates suggests that excess dCTP enhances replication while excess of dTTP inhibits replication. We therefore ask whether the increase in the dTTP/dCTP ration in mutagenized whole cells either contributes to or prolongs induced inhibition of replication. In addition we proposed that such an induced dNTP imbalance may also contribute to an increase in mutations by enhancing the probability for base-misincorporation.
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D006224:Cricetinae; D003412:Cricetulus; D003845:Deoxycytosine Nucleotides / Q000378:metabolism* / Q000528:radiation effects; D005260:Female; D007700:Kinetics; D009153:Mutagens / Q000494:pharmacology*; D010053:Ovary; D013463:Sulfuric Acid Esters / Q000494:pharmacology*; D013464:Sulfuric Acids / Q000494:pharmacology*; D013942:Thymine Nucleotides / Q000378:metabolism* / Q000528:radiation effects; D014466:Ultraviolet Rays
D003845:Deoxycytosine Nucleotides; D009153:Mutagens; D013463:Sulfuric Acid Esters; D013464:Sulfuric Acids; D013942:Thymine Nucleotides; C024107:2'-deoxycytidine 5'-triphosphate; C007482:dimethyl sulfate; C024157:thymidine 5'-triphosphate