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International Journal of Toxicology
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Studies of Strain Differences in the Spontaneous and Induced Frequencies of Cells Resistant to Calcium-Induced Terminal Differentiation

Robert T. Przygoda

Exxon Biomedical Sciences, Inc., East Millstone, New Jersey, USA

Richard H. McKee

Exxon Biomedical Sciences, Inc., East Millstone, New Jersey, USA

James J. Freeman

Exxon Biomedical Sciences, Inc., East Millstone, New Jersey, USA

Robert T. Plutnick

Exxon Biomedical Sciences, Inc., East Millstone, New Jersey, USA

Mark J. Nicolich

Exxon Biomedical Sciences, Inc., East Millstone, New Jersey, USA

Stanley Katz

C3H mice were found to be much less responsive to tumor induction in an initiation/promotion protocol than CD-I mice. To explore the difference in strain sensitivity, the frequencies of cells resistant to calcium-induced terminal differentiation(calcium resistant cells, CRCs) were measured in C3H, CD-I, and SENCAR mice. The induced frequencies after 7,12-dimethylbenz(a)anthracene(DMBA) treatment were similar in all three strains, ranging from 0.70 to 0.83 x 10-6, and suggested that the differences in tumor outcome were more likely related to promotion than initiation. Spontaneous frequencies ranged from 0.73 to 3.75 CRCs per mouse or 0.07 to 0.22 CRC/106 cells. The spontaneous frequency in the C3H mouse was significantly less than that in the other two strains. However, the spontaneous mutation rates were found to be similar in all three strains, ranging from 0.05 to 0.07 x 10-6 and it was found that the keratinocytes, which were resistant to terminal differentiation, were independently distributed in C3H but not in CD-I and SENCAR mice. These data are consistent with the hypothesis that clonal expansion occurs in CD-I and SENCAR but not C3H mice. Conceivably the greater propensity for clonal expansion in CD-I and SENCAR than in C3H mice is related to the greater likelihood of tumor formation as well as the more rapid development of tumors in the former strains.

Key Words: Initiation • Keratinocytes • Mutation • Promotion • Spontaneous Frequency

International Journal of Toxicology, Vol. 18, No. 1, 41-47 (1999)
DOI: 10.1080/109158199225792
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