Effect of folate deficiency on mutations at the hprt locus in Chinese hamster ovary cells exposed to monofunctional alkylating agents.
Multiplex PCR amplification of hprt exons from 113 Chinese hamster ovary cell clones selected for resistance to 6-thioguanine was performed to investigate the molecular basis for the synergistic mutagenic effects of nutritional folic acid deficiency and alkylating agents. In cells treated with ethyl methanesulfonate, intragenic deletions were detected in 9 of 46 (19.6%) clones derived from folate-deficient cells, but in none of 16 mutants grown in folate-replete medium. The number of deletions found in mutants generated by N-nitroso-N-ethylurea was low in both folate-deficient (1 of 25; 4%) and folate-replete (1 of 26; 3.8%) cells. Correction of folate deficiency may decrease the frequency of intragenic deletions caused by some alkylating agents.
Branda
R F
RF
Department of Medicine and the Vermont Cancer Center, University of Vermont, Burlington 05401, USA.
Lafayette
A R
AR
O'Neill
J P
JP
Nicklas
J A
JA
D000477:Alkylating Agents / Q000494:pharmacology*; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D005020:Ethyl Methanesulfonate / Q000494:pharmacology; D005038:Ethylnitrosourea / Q000494:pharmacology; D005494:Folic Acid Deficiency / Q000235:genetics*; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D009154:Mutation; D016133:Polymerase Chain Reaction; D013866:Thioguanine / Q000494:pharmacology
D000477:Alkylating Agents; D005020:Ethyl Methanesulfonate; D007041:Hypoxanthine Phosphoribosyltransferase; D013866:Thioguanine; D005038:Ethylnitrosourea