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 shwon 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 replicate cultures. N‐methyl‐N 1 ‐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.