DETECTION OF NON-MUTAGENIC CARCINOGENS USING CULTURED SYRIAN HAMSTER EMBRYO CELLS

TAKEKI TSUSUI1 AND J. CARL BARRETT2
1Department of Pharmacology, School of Dentistry at Tokyo, The Nippon Dental University, 1-9-20, Fujimi, Chiyoda-ku, Tokyo 102, Japan; 2National Institute of Environmental Health Sciences, P. O. Box 12233, Research Triangle Park, NC27709, U.S.A

AATEX 1(2):65-73


Abstract
The Syrian hamster embryo (SHE) cell transformation assay has a high predictive value (> 90 %) for the detection of carcinogens, including a number of non-mutagenic carcinogens". To validate the assay further, we examined the abilities of 17 chemicals, which were negatived in the Salmonella/microsome assay, to induced morphological transformation of SHE cells.
SHE cells (2.5 x 106) in tertiary cultures were plated in 75 cm2 flasks and treated with the chemicals for 48 hours. Following trypsinization, the cells were replated on 100 mm dishes at 2,000-3,000 cells per dish and allowed to form colonies for 7 additional days. Eleven of the 17 chemicals tested are reported to be carcinogenic in rodents (no data are available for 4 chemicals). Ten of the eleven chemicals induced morphological transformation of SHE cells. SHE cell transformation responses for other chemicals by other investigators also showed a positive transforming activity in agreement with the rodent carcinogenicity data. These results indicate a good correlation between induction of SHE cell transformation and carcinogenicity, suggesting that the SHE cell assay system could be useful for mechanistic studies and detection of potential carcinogenic activity of non-mutagenic carcinogens. The possible involvement of genetic mechanisms in cell transformation by these chemicals will be discussed.

Key words: cell transformation, non-mutagenic carcinogens, Syrian hamster embryo cells.


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