Podophyllotoxin resistance: a codominant selection system for quantitative mutagenesis studies in mammalian cells

Mutants resistant to the microtubule inhibitor podophyllotoxin (PodR), a codominant marker, can be readily selected in various mammalian cell lines such as, CHO, HeLa, mouse L cells, Syrian hamster cells (BHK21) and a mouse teratocarcinoma cell line OC15. In CHO cells, the recovery of PodR mutants is not affected by cell density (up to 1 X 10(6) cells per 100-mm diameter dish), and after treatment with the mutagen ethyl methanesulfonate maximum mutagenic effect is achieved after a relatively short expression time (40-48 h). The frequency of PodR mutants in various cell lines increased in a dose-dependent manner in response to treatment with the mutagens ethyl methanesulfonate and N-methyl-N'-nitro-N-nitrosoguanidine. The PodR selection system thus provides a new genetic marker which should prove useful in studies of quantitative mutagenesis in mammalian cells.