Spontaneous mutation rates of tumorigenic and nontumorigenic Chinese hamster embryo fibroblast cell lines.
The genomic stability of a series of nontumorigenic, tumorigenic, and tumor-derived Chinese hamster embryo fibroblastic (CHEF) cell lines was compared by examining their rates of spontaneous mutation at the hypoxanthine-guanine phosphoribosyl transferase (hprt) locus, using thioguanine resistance for selection of mutants. The spontaneous mutation rates were 1.1 x 10(-6) mutations/cell/generation in the non-tumor-forming CHEF/18 cell line and 4.9 x 10(-6) in the tumorigenic CHEF/16 cells. Three tumorigenic and tumor-derived CHEF cell lines derived from CHEF/18 (J132 3-2 T3L, focus 2, focus 3) and two lines (16-2 Tuk 4 and 204 Bu50 Tuk 2) derived from CHEF/16 were chosen on the basis of their karyotypes, which demonstrated a considerable level of chromosomal rearrangement. Mutation rates of four of these five lines ranged from 1.2 x 10(-6) to 8.9 x 10(-6) mutations per cell per generation. Only the fifth line, 16-2 Tuk 4, showed a significantly elevated rate of mutation as compared with the nontumorigenic CHEF/18 cell line. Thus, we have found no simple correlation between spontaneous mutation rate and the malignant phenotype, and we conclude that mutation rate per se is not a sensitive index of malignancy. In addition, we have compared three methods of calculating mutation rate and find that they rank the cell lines in the same order, but each stresses a different aspect of the distribution and therefore produces different estimates of the mutation rate.
Kaden
D
D
Division of Cancer Genetics, Dana-Farber Cancer Institute, Boston, Massachusetts 02115.
Gadi
I K
IK
Bardwell
L
L
Gelman
R
R
Sager
R
R
D000818:Animals; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D006224:Cricetinae; D003412:Cricetulus; D004351:Drug Resistance; D004622:Embryo, Mammalian; D005347:Fibroblasts / Q000166:cytology; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D009154:Mutation; D013866:Thioguanine / Q000494:pharmacology; D014178:Translocation, Genetic
D007041:Hypoxanthine Phosphoribosyltransferase; D013866:Thioguanine