Genotoxicity of trans-anethole in vitro.
Trans-anethole genotoxicity has been evaluated previously both in vitro and in vivo. To ascertain the reproducibility and relevance of previously conducted gene mutation studies, the Salmonella/microsome test and the L5178Y mouse lymphoma TK+/- assay were repeated according to the protocols that previously produced positive results. For the mouse lymphoma TK+/- assay, standard conditions were employed. For the Salmonella/microsome tests, however, metabolic cofactors were supplemented relative to standard protocols. In addition, trans-anethole was evaluated for its ability to induce chromosome aberrations in vitro in Chinese hamster ovary cells. The results presented here indicate that trans-anethole does not increase the mutant frequency in the Salmonella/microsome test, whereas a dose-related response was confirmed in the L5178Y mouse lymphoma TK+/- assay with metabolic activation. The metabolic conditions used in each of the published gene mutation assays may explain the various responses to trans-anethole. Trans-anethole did not induce chromosome aberrations in Chinese hamster ovary cells. The molecular nature of the genetic change induced in mouse lymphoma cells by trans-anethole has not been identified but the available genotoxicity data are consistent with either a recombination event or a non-DNA reactive mechanism. Considering the trans-anethole genotoxicity data base as a whole, including the positive response observed only in the L5178Y mouse lymphoma TK+/- assay, the irreproducible response in the Salmonella/microsome test, the negative result in the chromosome aberration test in vitro and the results from 32P-postlabeling studies in vivo, as well as the occurrence of liver tumors in the rat bioassay only at doses which exceeded the MTD and caused significant liver toxicity, repeated toxic insult followed by compensatory cell proliferation is favored as an underlying mechanism for the observed rat tumorigenic response.
Gorelick
N J
NJ
Procter & Gamble Company, Miami Valley Laboratories, Cincinnati, OH 45253-8707.
D000081248:Allylbenzene Derivatives; D000818:Animals; D000840:Anisoles / Q000633:toxicity*; D001711:Biotransformation; D016466:CHO Cells / Q000187:drug effects; D002869:Chromosome Aberrations; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D005421:Flavoring Agents / Q000633:toxicity*; D007940:Leukemia L5178; D051379:Mice; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D009249:NADP / Q000378:metabolism; D015203:Reproducibility of Results; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000081248:Allylbenzene Derivatives; D000840:Anisoles; D005421:Flavoring Agents; D009153:Mutagens; D009249:NADP; C006578:anethole