Identification of phenols of 7,12-dimethylbenz[a]anthracene by conversion into their methyl ethers

The compound 7,12-dimethylbenz[a]anthracene (DMBA), a powerful chemical carcinogen, undergoes enzymatic oxidation to a variety of metabolites. Phenols, the monohydroxylated derivatives of DMBA, are an electrophilic species capable of binding covalently with DNA. Although phenols may play a role in carcinogenesis, little information is available regarding these metabolites, many of which are chemically unstable and elusive to quantitative analysis. In this study, a method is described for the methylation of phenolic products to their chemically stable methyl ether derivatives. Application of this procedure to in vitro incubations of DMBA with rat liver microsomes resulted in the isolation and identification of 4-hydroxy DMBA, 8-hydroxy DMBA and 3-hydroxy DMBA.