Cigarette Smoke Radicals and the Role of
Free Radicals in Chemical Carcinogenicity
William A. Pryor
Biodynamics Institute, Louisiana State University,
Baton Rouge, Louisiana
Abstract
This article consists of two parts: a brief overview of the ways in which free radicals can be involved in chemical carcinogenesis, and a review of cigarette smoke chemistry. Carcinogenesis is generally agreed to involve at least three stages: initiation, promotion, and progression. It is suggested that radicals sometimes are involved in the initiation step, either in the oxidative activation of a procarcinogen (such as benzo[a]pyrene) to its carcinogenic form or in the binding of the carcinogenic species to DNA, or both. The fraction of initiation events that involve radicals, as opposed to two-electron steps, is not known, but radicals probably are involved in a substantial number, although probably not a majority, of cancer initation reactions. Promotion always involves radicals, at least to some extent. Progression probably does not normally involve radicals. The second part of this article reviews the molecular mechanisms involved in cigarette-induced tumors, particularly by aqueous cigarette tar (ACT) extracts and by a model of these solutions, aged solutions of catechol. ACT solutions as well as aged solutions of catechol contain a quinone-hydroquinone-semiquinone system that can reduce oxygen to produce superoxide and hence hydrogen peroxide and the hydroxyl radical. Both the cigarette tar radical and the catechol-derived radical can penetrate viable cells, bind to DNA, and cause nicks. -- Environ Health Perspect 105(Suppl 4):875-882 (1997)
Key words: adduct, cigarette, DNA, electron transfer, initiation, oxidation, promotion, radical, smoke, superoxide
This paper is based on a presentation at the symposium on Mechanisms and Prevention of Environmentally Caused Cancers held 21-25 October 1995 in Santa Fe, New Mexico. Manuscript received at EHP 16 April 1996; accepted 26 August 1996.
Address correspondence to Dr. W.A. Pryor, Biodynamics Institute, 711 Choppin Hall, Louisiana State University, Baton Rouge, LA 70803. Telephone: (504) 388-2063. Fax: (504) 388-4936. E-mail: wpryor@unix1.sncc
Abbreviations used: ACT, aqueous cigarette tar extracts; B[a]P, benzo[a]pyrene; DMPO, 5,5-dimethyl-1-pyrroline-N-oxide; ESR, electron spin resonance (also called electron paramagnetic resonance); PAH, polycyclic aromatic hydrocarbon; PAM, pulmonary alveolar macrophage; SOD, superoxide dismutase.
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Last Update: June 19, 1997