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Fluctuation tests of the Luria-Delbruck type have been used to examine the frequency of spontaneous variations in cultures of diploid, tetraploid, and octaploid Chinese hamster cells. Resistance to 8-azaguanine and altered response to thermal shock were chosen as marker systems. Mutation frequencies of approximately 10-e and have been estimated for heat resistance and azaguanine resistance respectively. Rates of mutation for these markers remain constant or decline slightly in cells with increasing numbers of chromosome sets. This trend is not in accordance with expectations based on the assumption of dominant, co-dominant, or recessive changes at gene or chromosome levels. It is suggested that at least some variations may arise in somatic cells by stable shifts in phenotypic expression rather than by changes in genetic information.

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Selectivity in Chinese hamster cells with antimycin A and chloramphenicol depends on a metabolic balance which can be modulated by varying the level of exogenous pyruvate. The effects of both inhibitors are most clearly seen in pyruvate-free nutrients. Addition of 1 mM pyruvate in plating assays shifts dose-response curves for antimycin A or chloramphenicol to higher concentration levels and reduces the differential in response between sensitive and resistant cells. In mass populations, growth inhibition by antimycin A is reduced by adding pyruvate, and growth curves for sensitive and resistant cells tend to converge. These observations show that responses to antimitochondrial drugs can be conditioned by extrinsic factors and indicate the need for further definition of selective systems.