title: Mutagenic metabolites of benzene detected in the Microscreen assay.
abstract: The reactive metobolite responsible for benzene hematotoxicity and carcinogenicity is unknown. It can be hypothesized that the ultimate carcinogen derived from benzene metabolism might also act as a mutagen. This laboratory has recently developed a new assay that can detect mutagens of all types, using a single strain of bacteria, E. coli WP2s (lambda), as a target. Different genetic end points can be monitored in the same exposed population of bacteria. When a number of known metabolites of benzene were assayed, only trans,trans-muconic acid gave a strong positive response. Mutations were induced at two genetic loci (Trp+ revertants and T5 resistance). The mutagenic activity was greatly increased when a rat liver metabolizing system was added. We speculate that trans,trans-muconic acid is metabolized to a diepoxide, which may be the ultimate mutagen and possibly the ultimate carcinogen.
authors.affiliation: Institute of Environmental Medicine, New York University Medical Center, NY 10016.
authors.forename: R G
authors.initials: RG
authors.lastname: Rossman
authors.forename: C B
authors.initials: CB
authors.lastname: Klein
authors.forename: C A
authors.initials: CA
authors.lastname: Snyder
mesh_terms: D000818:Animals; D001554:Benzene / Q000378:metabolism* / Q000633:toxicity; D001711:Biotransformation; D004926:Escherichia coli / Q000235:genetics; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism; D009152:Mutagenicity Tests; D009153:Mutagens / Q000378:metabolism*; D051381:Rats; D013011:Sorbic Acid / Q000031:analogs & derivatives / Q000633:toxicity
chemical_list: D009153:Mutagens; C005939:muconic acid; D001554:Benzene; D013011:Sorbic Acid