Environmental Health Perspectives 105, Supplement 5, September 1997

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Mechanism of Asbestos-mediated DNA Damage: Role of Heme and Heme Proteins

Qamar Rahman, 1 Nayyara Mahmood, 1 Sikander G. Khan, 2 Jamal M. Arif, 3 and Mohammad Athar 4

1 Industrial Toxicology Research Centre, Lucknow, India
2 National Institutes of Health, Bethesda, Maryland
3 Department of Preventive Medicine and Environmental Health, University of Kentucky, Lexington, Kentucky
4 Department of Medical Elementology and Toxicology, Hamdard University, New Delhi, India

Abstract
Several observations, including studies from this laboratory, demonstrate that asbestos generates free radicals in the biological system that may play a role in the manifestation of asbestos-related cytotoxicity and carcinogenicity. It has also been demonstrated that iron associated with asbestos plays an important role in the asbestos-mediated generation of reactive oxygen species. Exposure to asbestos leads to degradation of heme proteins such as cytochrome P450-releasing heme in cytosol. Our simulation experiments in the presence of heme show that such asbestos-released heme may increase lipid peroxidation and can cause DNA damage. Further, heme and horseradish peroxidase (HRP) can cause extensive DNA damage in the presence of asbestos and hydrogen peroxide/organic peroxide/hydroperoxides. HRP catalyzes oxidation reactions in a manner similar to that of prostaglandin H synthetase. Iron released from asbestos is only partially responsible for DNA damage. However, our studies indicate that DNA damage mediated by asbestos in vivo may be caused by a combination of effects such as the release and participation of iron, heme, and heme moiety of prostaglandin H synthetase in free radical generation from peroxides and hydroperoxides. -- Environ Health Perspect 105(Suppl 5):1109-1112 (1997)

Key words : asbestos-DNA, heme, heme protein, heme peroxides

This paper is based on a presentation at The Sixth International Meeting on the Toxicology of Natural and Man-Made Fibrous and Non-Fibrous Particles held 15-18 September 1996 in Lake Placid, New York. Manuscript received at EHP 26 March 1997; accepted 15 July 1997.

Address correspondence to Dr. Q. Rahman, Fiber Toxicology Division, Industrial Toxicology Research Centre, Post Box No. 80, M.G. Marg, Lucknow, 226 001, India. Telephone: 91 522 283474. Fax: 91 522 228227. E-mail: intox@itrc.sirnetd.emet.in

Abbreviations used: ABIN, 2,2´-azobis(isobutyronitrile); BOOB, benzoyl peroxide; COOH, cumene hydroperoxide; H 2 O 2 , hydrogen peroxide; HRP, horseradish peroxidase, ROS, reactive oxygen species; tert-BOOH, tertiary-butyl hydroperoxide.

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Last Update: October 28, 1997