Comparative evaluation of genetic toxicity patterns of carcinogens and noncarcinogens: strategies for predictive use of short-term assays.
The results of a recent comprehensive evaluation of the relationship between four measures of in vitro genetic toxicity and the capacity of the chemicals to induce neoplasia in rodents carry some important implications. The results showed that while the Salmonella mutagenesis assay detected only about half of the carcinogens as mutagens, the other three in vitro assays (mutagenesis in MOLY cells or induction of aberrations or SCEs in CHO cells) did not complement Salmonella since they failed to effectively discriminate between the carcinogens and noncarcinogens found negative in the Salmonella assay. The specificity of the Salmonella assay for this group of 73 chemicals was relatively high (only 4 of 29 noncarcinogens were positive). Therefore, we have begun to evaluate in vivo genetic toxicity assays for their ability to complement Salmonella in the identification of carcinogens.
Tennant
R W
RW
National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709.
Spalding
J W
JW
Stasiewicz
S
S
Caspary
W D
WD
Mason
J M
JM
Resnick
M A
MA
D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D002869:Chromosome Aberrations; D006224:Cricetinae; D004330:Drosophila; D004353:Drug Evaluation, Preclinical; D005260:Female; D008297:Male; D051379:Mice; D009152:Mutagenicity Tests; D009369:Neoplasms / Q000139:chemically induced*; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects; D012737:Sex Factors; D012854:Sister Chromatid Exchange / Q000187:drug effects; D013045:Species Specificity
D002273:Carcinogens