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Divisions of Cancer Genetics [D. K., L. B., R. S.] and Biostatistics and Epidemiology [R. G.], Dana-Farber Cancer Institute, Boston, Massachusetts 02115; Department of Surgery, UMDNJ, RWJ Medical School, Brunswick, NJ 08903 [I. K.]
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-tumorforming 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 32 T3L, focus 2, focus 3) and two lines (162 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.
1 Supported by NIH Grant CA-39814.
2 Present address: Meta Systems, Inc., 58 Charles Street, Cambridge, MA 02141.
3 Present address: University of California, Stanford, CA 94305.
4 To whom requests for reprints should be addressed.
Received 4/ 5/88. Revised 2/16/89. Accepted 3/17/89.
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