New studies on trans-anethole oxide and trans-asarone oxide.
The widespread use of naturally occurring alkenylbenzenes as flavoring and fragrance agents has led to a long-standing interest in their toxicity and carcinogenicity. Among them several allyl- and propenylbenzenes have been found to be mutagenic and carcinogenic. It has been shown that the carcinogenicity of several allylbenzenes can be related to the formation of electrophilic sulfuric acid esters following 1'-hydroxylation. Unlike the allylbenzenes, the mechanisms of carcinogenesis of propenylbenzenes such as anethole and asarone are not clear. It has been reported that one of the main metabolic pathways of trans-anethole is the epoxidation of the side chain 1,2-double bond, which was responsible for cytotoxicity but not for genotoxicity. However, we report here that synthetic trans-anethole oxide prepared from trans-anethole and dimethyldioxirane is not only mutagenic for Salmonella tester strains but is also carcinogenic in the induction of hepatomas in B6C3F1 mice and skin papillomas in CD-1 mice. Synthetic trans-asarone oxide was also carcinogenic in the induction of hepatomas as well as mutagenic for Salmonella strains. Further studies are needed on these side chain oxides of trans-anethole and trans-asarone as possible metabolites in the toxicity, mutagenicity and carcinogenicity of these and other propenylbenzenes.
Kim
S G
SG
McArdle Laboratory for Cancer Research, School of Medicine, University of Wisconsin, Madison, WI 53706, USA.
Liem
A
A
Stewart
B C
BC
Miller
J A
JA
D000081248:Allylbenzene Derivatives; D000818:Animals; D000840:Anisoles / Q000737:chemistry / Q000633:toxicity*; D015197:Carcinogenicity Tests; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced*; D005260:Female; D008113:Liver Neoplasms / Q000139:chemically induced*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009152:Mutagenicity Tests; D010087:Oxides / Q000737:chemistry / Q000633:toxicity*; D010212:Papilloma / Q000139:chemically induced*; D012486:Salmonella typhimurium / Q000187:drug effects; D012878:Skin Neoplasms / Q000139:chemically induced*
D000081248:Allylbenzene Derivatives; D000840:Anisoles; D010087:Oxides; C120686:asarone oxide; C120685:anethole oxide