Mutagenic metabolites of benzene detected in the Microscreen assay.

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.