The mutational origin of serum independence in Chinese hamster cells in vitro

The genetic mechanisms determining the ability of transformed cells to grow in a medium with a low serum content (ser+) were studied in a clone of Chinese hamster cells with normal serum requirements. The fluctuation test has shown that serum independence occurs as a random spontaneous event. Its rate of occurrence is about 10(-5). The concomitant study of a gene mutation (resistance to 6-mercaptopurine--6MP) revealed similar characteristics with respect to the distribution of the number of mutants in replicative cultures. N-methyl-N1-nitro-N-nitrosoguanidine (MNNG) and SV40 significantly increased the frequency of ser+ colonies. Induction was detected after an expression time of 3-4 days, which is typical of gene mutations. In 16 out of 18 ser+ clones of independent origin the ser+ character remained stable. The results suggest that the ser+ character originates in most cases from a mutation event.