28622-66-4Relevant academic research and scientific papers
Analysis of phenanthrene and benzo[ a ]pyrene tetraol enantiomers in human urine: Relevance to the bay region diol epoxide hypothesis of benzo[ a ]pyrene carcinogenesis and to biomarker studies
Hecht, Stephen S.,Carmella, Steven G.,Villalta, Peter W.,Hochalter, J. Bradley
body text, p. 900 - 908 (2011/03/17)
One widely accepted metabolic activation pathway of the prototypic carcinogenic polycyclic aromatic hydrocarbon (PAH) benzo[a]pyrene (BaP) proceeds through the "bay region diol epoxide" BaP-(7R,8S)-diol-(9S,10R)- epoxide (2). However, few studies have addressed the analysis of human urinary metabolites of BaP, which result from this pathway. Phenanthrene (Phe) is structurally related to BaP, but human exposure to Phe is far greater, and its metabolites can be readily detected in urine. Thus, Phe metabolites have been proposed as biomarkers of PAH exposure and metabolic activation. Phe-tetraols in particular could be biomarkers of the diol epoxide pathway. While BaP-tetraols and Phe-tetraols have been previously quantified in human urine, no published studies have determined their enantiomeric composition. This is important because different enantiomers would result from the bay region diol epoxide and "reverse" diol epoxide pathways, the latter being associated with weak mutagenicity and carcinogenicity. We addressed this problem using chiral HPLC to separate the enantiomers of BaP-7,8,9,10-tetraol and Phe-1,2,3,4-tetraol. Urine samples from smokers were subjected to solid-phase extraction, chiral HPLC, and GC-NICI-MS/MS analysis for silylated Phe-1,2,3,4-tetraols. The results demonstrated that >96% of Phe-1,2,3,4-tetraol in smokers urine was Phe-(1S,2R,3S,4R)-tetraol (12), resulting from the "reverse" diol epoxide pathway, whereas less than 4% resulted from the "bay region diol epoxide" pathway of Phe metabolism. Urine from creosote workers was similarly analyzed for BaP-7,8,9,10-tetraol enantiomers. In contrast to the results of the Phe-tetraol analyses, 78% of BaP-7,8,9,10-tetraol in these human urine samples was BaP-(7R,8S,9R,10S)-tetraol (3) resulting from the "bay region diol epoxide" pathway of BaP metabolism. These results provide further support for the bay region diol epoxide pathway of BaP metabolism in humans and demonstrate differences in BaP and Phe metabolism, which may be important when considering Phe-tetraols as biomarkers of PAH metabolic activation.
Synthesis of the o-Quinones and Dihydro Diols of Polycyclic Aromatic Hydrocarbons from the Corresponding Phenols
Sukumaran, K.B.,Harvey, Ronald G.
, p. 4407 - 4413 (2007/10/02)
Terminal-ring trans-dihydro diol metabolites have been implicated as the ultimate carcinogenic forms of polycyclic aromatic hydrocarbons.Synthesis of these dihydro diols from the related polycyclic phenols in two steps via oxidation to the corresponding o-quinones with either Fremy's salt or phenylseleninic anhydride followed by stereospecific reduction with lithium aluminum hydride is described.The non-K-region quinones and trans-dihydro diols of naphthalene, anthracene, phenanthrene, benzanthracene, benzopyrene, and 7,12-dimethylbenzanthracene are synthesized via this approach.Although poor yields (1-4percent) were previously reported for the reduction of non-K-region quinones, an improved experimental procedure has been developed which affords the trans-dihydro diols free of the isomeric cis-dihydro diols in generally good yields.Major byproducts are the corresponding hydroquinones, previously undetected, and the related tetrahydro diols.The latter are the major products of reduction of the poorly soluble quinones of benzopyrene and benzanthracene and are shown to arise through further reduction of the dihydro diols.Since the tetrahydro diols are convertible to dihydro diols and the hydroquinones are reoxidizable to quinones, good overall conversions of quinones to dihydro diols are attainable. trans-3,4-Dihydroxy-3,4-dihydro-7,12-dimethylbenzanthracene synthesized in these studies is the most potent tumorigenic hydrocarbon metabolite tested to date.
