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

Abstract

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.

Branching Processes in Biology

“…Figure 6.6 includes the data of Morrow (1970) and Fig. 6.7 shows the data of Varshaver et al (1983). Figures 6.6 and 6.7 demonstrate that the r and P 0 values obtained in this way, are not matched by the r − P 0 plots of the Luria-Delbrück, Galton-Watson, and Markov branching process models (from left to right).…”

“…The typical estimates of the first-stage forward mutation rate are α 01 ≈ 10 −6 . The corresponding reversal Varshaver et al 1983), and the r − P 0 plots (N = 10 5 ) of the Galton-Watson, Luria-Delbrück and Markov branching process models (from left to right). (Source: Kimmel and Axelrod 1994) rates are α 10 ≈ 0.2 − 0.95.…”

Gradient Method for Finding Optimal Scheduling in Infinite Dimensional Models of Chemotherapy

“…A number of researchers have carried out the procedure to estimate rates of emergence and evolution of resistance (by gene amplification and other means) (Morrow, 1970;Varshaver et al, 1983;Murnane and Yezzi, 1988;Tlsty et al, 1989), obtaining estimates of the mutation probabilities, per cell division, in the range from lovX to 1W6, with generally higher estimates for tumorogenic than for "normal" cells. The data from the above papers were re-analyzed in a recent paper by Kimmel and Axelrod (19941, using a two-stage model of mutation.…”