Metabolism of benz[a]anthracene by the filamentous fungus Cunninghamella elegans

Abstract

The metabolism of the carcinogen benz[a]anthracene (BA), a tetracyclic aromatic hydrocarbon, by Cunninghamella elegans was investigated. C. elegans grown on Sabouraud dextrose broth transformed [14C]BA to labeled BA trans- 8,9-dihydrodiol (90%), BA trans-10,11-dihydrodiol (6%), and BA trans-3,4- dihydrodiol (4%), but not to BA trans-5,6-dihydrodiol. These metabolites were separated by thin-layer chromatography and reversed-phase high-performance liquid chromatography and were identified by UV and mass spectral techniques. A BA tetraol, 8β,9α, 10α,11β-tetrahydroxy-8α,9β,10β,11α-tetrahydro- BA, was also identified as a metabolite and may have arisen as an additional oxidation product of either BA, 8,9- or 10,11-dihydrodiol. This is the first study in which a biologically produced BA tetraol has been identified. Our results suggest that the transformation of BA to trans-dihydrodiols by C. elegans is similar to the transformation of BA found in mammals, except that BA 5,6-dihydrodiol is not produced.