Role of oxygen radicals in induction of DNA damage by metabolites of benzene.
Benzene is strongly suspected of being an animal and human carcinogen, but the mechanisms by which benzene induces tumors of lymphoid and hematopoietic organs are unknown. Binding studies in vivo suggest a very low level of covalent binding to the DNA of bone marrow elements. Since several metabolites of benzene have the potential to undergo autooxidation and thereby generate reactive oxygen intermediates, we have tested the hypothesis that benzene metabolites can induce DNA damage through the generation of oxygen radicals. Hydroquinone (HQ), benzoquinone (BQ), catechol, and 1,2,4-benzenetriol (BT) were first tested for their ability to generate O2-. at a physiological pH. BT, and to a lesser extent HQ, were autooxidized and produced significant quantities of O2-.. No detectable O2-. was produced by catechol or BQ. Similarly, BT was very efficient at degrading DNA, and this degradation was inhibited by scavengers of O2-., H2O2 and .OH. HQ did not degrade DNA but did induce single- and double-strand breaks. In contrast to the action of BT, the breakage of DNA by HQ was not inhibited by scavengers of reactive oxygen intermediates. The metabolites which did not produce O2-. (catechol and BQ) did not induce significant breakage of DNA. Taken together, the data support the hypothesis that certain benzene metabolites can induce DNA damage through the production of oxygen radicals; they further suggest that other metabolites may act, via another mechanism, to damage DNA.
Lewis
J G
JG
Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710.
Stewart
W
W
Adams
D O
DO
D001554:Benzene / Q000378:metabolism*; D004247:DNA / Q000187:drug effects* / Q000378:metabolism; D004249:DNA Damage; D005609:Free Radicals; D006873:Hydroquinones / Q000633:toxicity*; D010100:Oxygen / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism
D005609:Free Radicals; D006873:Hydroquinones; D013481:Superoxides; C013038:hydroxyhydroquinone; D004247:DNA; D013482:Superoxide Dismutase; D001554:Benzene; D010100:Oxygen; C031927:hydroquinone