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Effect of Folate Deficiency on Mutations at the hprt Locus in Chinese Hamster Ovary Cells Exposed to Monofunctional Alkylating Agents¹

Department of Medicine and the Vermont Cancer Center, University of Vermont, Burlington, Vermont 05401

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.

¹ This work was supported by National Cancer Institute Grant CA 41843.

² To whom requests for reprints should be addressed, at Genetics Laboratory, University of Vermont, 32 North Prospect Street, Burlington, VT 05401.

Received 4/14/97. Accepted 5/15/97.

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