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Relationships of quantum mechanical calculations, relative mutagenicity of benzo(a)anthracene diol epoxides, and ''Bay Region'' concept of aromatic hydrocarbon carcinogenicity

Journal Article · · J. Toxicol. Environ. Health; (United States)

Evidence supporting the conclusion that 7,8-dihydroxy-9,10-epoxy-7,8,9, 10-tetrahydrobenzo(a)pyrenes are ultimate mutagenic and carcinogenic forms of benzo(a)pyrene (BP) is summarized. Quantum mechanical calculations that predict reactivity of diol epoxides derived from BP and other polycyclic aromatic hydrocarbons are described. The calculations predict that diol epoxides in which the oxirane ring forms part of a ''bay region'' of a tetrahydrobenzo ring should be the most reactive for a given aromatic hydrocarbon. Experiments with dihydrodiols and diol epoxides from benzo(a)anthracene (BA) are described. The ability to metabolically activate BA 3,4-dihydrodiol to species much more mutagenic than those obtained from other BA dihydrodiols and the much greater mutagenicity of the diastereoisomeric 3,4-diol-1,2-epoxides of 1,2,3,4-tetrahydro BA relative to other diol epoxides of BA are in accord with predictions of the quantum mechanical calculations.

Research Organization:
National Inst. of Arthritis, Metabolism, and Digestive Diseases Bethesda, MD
OSTI ID:
5087230
Journal Information:
J. Toxicol. Environ. Health; (United States), Journal Name: J. Toxicol. Environ. Health; (United States) Vol. 2:6; ISSN JTEHD
Country of Publication:
United States
Language:
English