Chromosome aberration and sister chromatid exchange tests in Chinese hamster ovary cells in vitro. III. Results with 27 chemicals.
Twenty-seven chemicals previously tested in rodent carcinogenicity assays were tested for induction of chromosomal aberrations (ABS) and sister chromatid exchanges (SCE) in Chinese hamster ovary (CHO) cells as part of a larger analysis of the correlation between results of in vitro genetic toxicity assays and carcinogenicity bioassays. Chemicals were tested up to toxic doses with and without exogenous metabolic activation. Seventeen of the chemicals tested were carcinogens; only two of these were negative for both ABS and SCE. Of the eight noncarcinogens tested, four were negative for both endpoints (ABS and SCE) and four gave a positive response for at least one endpoint. Of the remaining two chemicals, one, diallyl phthalate, gave an equivocal response in the bioassay and a positive response in these CHO cell cytogenetics tests. The other chemical, 2,4-toluene diisocyanate, was tested for carcinogenicity as a mixture with the 2,6-isomer; the mixture was carcinogenic, but the cytogenetic test results for the 2,4-isomer were negative. Only six of the 27 chemicals tested produced an effect in one endpoint alone; the other 21 were either positive or negative for both ABS and SCE. Only one of the 27 chemicals tested required S9 for a positive response in the SCE test; two chemicals required S9 for a positive result in the ABS test. Experiments with unsynchronized CHO cells demonstrated that mean SCE frequency increased with increasing culture time, and this may have been a factor in the positive results obtained for five chemicals in the SCE test under conditions of delayed harvest.
Gulati
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DK
Environmental Health Research and Testing, Inc., Lexington, Kentucky.
Witt
K
K
Anderson
B
B
Zeiger
E
E
Shelby
M D
MD
D000818:Animals; D001711:Biotransformation; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000633:toxicity; D002460:Cell Line; D055598:Chemical Phenomena; D002621:Chemistry; D002869:Chromosome Aberrations; D006224:Cricetinae; D008099:Liver / Q000378:metabolism; D008297:Male; D009152:Mutagenicity Tests; D009153:Mutagens / Q000493:pharmacokinetics / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D012854:Sister Chromatid Exchange
D002273:Carcinogens; D009153:Mutagens