Differences in Mitotic Control among Mammalian Cells

For a number of years, our laboratory has been studying gene amplification in rodent cell lines as a mechanism for acquired resistance. We have found that prior treatment with various agents that perturb DNA synthesis (γ and UV radiation, inhibitors of DNA synthesis, carcinogens, and hypoxia) can enhance frequencies of gene amplification. Common features of these treatments include extensive cell killing and extensive chromosome damage, in addition to a higher frequency of gene amplification among surviving cells (see Schimke 1988). Our finding (Sherwood et al. 1988) that inhibition of protein synthesis during the time of inhibition of DNA synthesis "protected" cells from cytotoxicity associated with inhibition of DNA synthesis and the generation of chromosome damage and abolished the enhanced gene amplification led us to conclude that the response to the induced perturbation was crucial in cell killing as well as other observed effects. We have further concluded that cytotoxicity associated...