Experiments on the effect of the medium in mutation tests with the HGPRT system in cultured mammalian cells

Higher mutation frequencies were observed on 8AG than on 6TG medium when HGPRT-deficient mutants were being selected in V79 Chinese hamster cells. 2 alternative explanations for the effect of the medium were considered, namely (1), that mechanisms are present that cause resistance to 8AG only, in addition to that (or those) causing resistance to both drugs, and (2), that mutants with low HGPRT content survive on 8AG but not on 6TG medium, owing to lower affinity of 8AG for the enzyme. The second explanation was favoured as a result of various experimental approaches, including kinetics of expression on the 2 media, cross-resistance at different expression times and serial selection on the 2 media.