The effects of pyrimidine nucleotides on alkylating agent induced cytotoxicity and spontaneous and induced mutation to purine analog resistance in V79 cells.
Exposure of three V79 cell lines to dT after treatment with monofunctional alkylating agents resulted in potentiation of alkylation induced cytotoxicity. The degree of potentiation achieved was dependent on the concentration and duration of exposure to dT and was reversed by equimolar concentrations of dCyd. Exposure to dT after UV or X-irradiation or treatment with HN2 or MMC did not affect the cytotoxic response. dT exposure at non-cytotoxic concentrations did not affect DNA synthesis as measured by [3H]-dT incorporation when allowance was made for reductions in specific activity of labelled thymidine. However, dT post treatment reversed the alkylation induced inhibition of DNA synthesis. Toxic concentrations of dT caused an increase in frequency of TGR colonies but this increase was shown to be due to effects of dT on cell growth rate, and differential sensitivity ot HGPRT- and HGPRT+ cells. The frequency of spontaneous and alkylation induced AZR and to a lesser extent TGR colonies was also increased by non-toxic dT concentrations. Evidence was obtained which suggests that this increase is more likely to be due to alterations in the selective efficiency of the purine analogs than alterations in coding fidelity due to altered dNTP pools.
D000477:Alkylating Agents / Q000494:pharmacology*; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D004247:DNA / Q000096:biosynthesis; D004351:Drug Resistance; D004357:Drug Synergism; D009154:Mutation; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011687:Purines / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism / Q000494:pharmacology*; D013942:Thymine Nucleotides / Q000378:metabolism
D000477:Alkylating Agents; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011687:Purines; D013942:Thymine Nucleotides; D002110:Caffeine; D004247:DNA; C024157:thymidine 5'-triphosphate; D013936:Thymidine