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Characterization of ([plus minus])-7,8,10-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene-9-sulfonate

Journal Article · · Chemical Research in Toxicology; (United States)
OSTI ID:6282341
;  [1]
  1. Univ. of Kansas Medical Center, Kansas City (United States)

The genotoxicity of certain benzo[a]pyrene (BP) derivatives is significantly enhanced in strains of Salmonella typhimurium following addition of sulfite to the incubations. The interaction between sulfite and those BP derivatives also results in the formation of isomeric BP sulfonates. As these trihydroxy sulfonates are formed in incubations of BP derivatives and sulfite in which a marked potentiation of bacterial mutagenicity occurs, we have investigated the properties of these novel intermediates. The compound ([plus minus])-7, 8, 10-trihydroxy-7, 8, 9, 10-tetrahydrobenzo[a]pyrene-9-sulfonate (BPT-9-sulfonate) was isolated and characterized in terms of its chemical and biological activity. The BPT sulfonate isomer is formed by the addition of the sulfite anion radical to the 9, 10-double bond of the known promutagen, ([plus minus])-7, 8-dihydroxy-7, 8-dihydrobenzo[a]pyrene (BP-7, 8-diol). Evidence for the free radical character of this addition includes the initiation of the reaction by either peroxidase-catalyzed or chemical one-electron oxidation of sulfite, the inhibition of the reaction by phenolic antioxidants, and the isolation and characterization of the chain termination product, 7, 8-dihydroxy-7, 8, 9, 10-tetrahydrobenzo[a]pyrene-9, 10-disulfonate (BPD-disulfonate). Analysis of incubations of S. typhimurium strain TA98 with BP-7, 8-diol and sulfite, which resulted in a 10-fold increase in revertant bacterial colonies above control levels, showed that BPT-9-sulfonate and BPD-disulfonate were the only isolable products derived from BP-7, 8-diol. This prompted a further investigation of the chemistry of these products. BPT-9-sulfonate was found to be quite stable in aqueous media, being refractory to acid- or base-catalyzed hydrolysis over a pH range of 3-11. Further, it was unreactive in aqueous incubations with a diverse range of chemical and biological nucleophiles of varying strengths.14 refs., 2 figs., 2 tabs.

OSTI ID:
6282341
Journal Information:
Chemical Research in Toxicology; (United States), Journal Name: Chemical Research in Toxicology; (United States) Vol. 5:6; ISSN 0893-228X; ISSN CRTOEC
Country of Publication:
United States
Language:
English