Catechol ortho-quinones: The electrophilic compounds that form depurinating DNA adducts and could initiate cancer and other diseases

Ercole L. Cavalieri, Kai Ming Li, Narayanan Balu, Muhammad Saeed, Prabu Devanesan, Sheila Higginbotham, John Zhao, Michael L. Gross, Eleanor G. Rogan

Research output: Contribution to journalArticle

174 Scopus citations

Abstract

Catechol estrogens and catecholamines are metabolized to quinones, and the metabolite catechol (1,2-dihydroxybenzene) of the leukemogenic benzene can also be oxidized to its quinone. We report here that quinones obtained by enzymatic oxidation of catechol and dopamine with horseradish peroxidase, tyrosinase or phenobarbital-induced rat liver microsomes react with DNA by 1,4-Michael addition to form predominantly depurinating adducts at the N-7 of guanine and the N-3 of adenine. These adducts are analogous to the ones formed with DNA by enzymatically oxidized 4-catechol estrogens (Cavalieri, E.L., et al. (1997) Proc. Natl Acad. Sci., 94, 10937). The adducts were identified by comparison with standard adducts synthesized by reaction of catechol quinone or dopamine quinone with deoxyguanosine or adenine. We hypothesize that mutations induced by apurinic sites, generated by the depurinating adducts, may initiate cancer by benzene and estrogens, and some neurodegenerative diseases (e.g. Parkinson's disease) by dopamine. These data suggest that there is a unifying molecular mechanism, namely, formation of specific depurinating DNA adducts at the N-7 of guanine and N-3 of adenine, that could initiate many cancers and neurodegenerative diseases.

Original languageEnglish (US)
Pages (from-to)1071-1077
Number of pages7
JournalCarcinogenesis
Volume23
Issue number6
DOIs
StatePublished - 2002

ASJC Scopus subject areas

  • Cancer Research

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