Synthesis of anti-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydro-11- methylbenzo[a]pyrene and its reaction with DNA

Jyh Ming Lin, Dhimant Desai, Lehua Chung, Stephen S. Hecht, Shantu Amin

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Substitution of a methyl group in the bay region can enhance the tumorigenicity of polycyclic aromatic hydrocarbons such as chrysene, benz[a]anthracene, and others. This phenomenon has been related to facile DNA adduct formation of bay region diol epoxides with a methyl group and epoxide ring in the same bay. While anti-7,8-dihydroxy-9,10-epoxy-7,8,9,10- tetrahydrobenzo[a]pyrene and its DNA adduct formation have been studied extensively, it is not known whether a methyl substituent in the bay region alters the reactivity of DNA in this system. This is of interest because 11- methylbenzo[a]pyrene, which has a bay region methyl group, is more tumorigenic than benzo[a]pyrene. To examine the question, we have devised and employed an efficient synthesis based on photochemical cyclization, and prepared anti-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydro-11- methylbenzo[a]pyrene, the likely ultimate carcinogen of 11- methylbenzo[a]pyrene. We have then reacted anti-7,8-dihydroxy-9,10- epoxy7,8,9,10-tetrahydro-11-methylbenzo[a]pyrene with calf thymus DNA and found that it gives three major adducts. These were identified as having resulted from cis- and trans-ring opening of the (S,R,R,S)-enantiomer and from trans-ring opening of the (R,S,S,R)-enantiomer. The standard deoxyguanosine adduct markers were prepared, and their structures were tentatively assigned on the basis of their CD and 1H NMR spectra. The adduct distribution of anti-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydro-11- methylbenzo[a]pyrene) is quite different from that observed in the reaction of DNA with the corresponding diol epoxides of benzo[a]pyrene or with 5- methylchrysene. The heterogeneity of adducts obtained with anti-7,8- dihydroxy-9,10-epoxy-7,8,9,10-tetrahydro-11-methylbenzo[a]pyrene thus may be related to the enhanced tumorigenicity of 11-methylbenzo[a]pyrene.

Original languageEnglish (US)
Pages (from-to)341-346
Number of pages6
JournalChemical research in toxicology
Issue number4
StatePublished - Apr 1999

All Science Journal Classification (ASJC) codes

  • Toxicology


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