74 research outputs found
Genotoxicity characteristics of reverse diol-epoxides of chrysene
Trans-3,4-dihydroxy-3,4-dihydrochrysene (chrysene-3,4-diol), a major metabolite of chrysene, is further metabolized by rat liver enzymes to products which effectively revert the his− Salmonella typhimurium strain TA98 to histidine prototrophy, but are only weakly mutagenic in strain TA100 and in Chinese hamster V79 cells (acquisition of resistance to 6-thioguanine). The liver enzyme mediated mutagenicity of chrysene-3,4-diol is substantially enhanced in the presence of 1,1,1-trichloropropene 2,3-oxide, an inhibitor of microsomal epoxide hydrolase. The predominant metabolites of chrysene-3,4-diol, namely the anti- and syn-isomers of its 1,2-oxide (termed reverse diol-epoxides), proved to be extraordinarily effective mutagens in S.typhimurium strain TA98, but were only moderately active in strains TA100 and TA104, and in the SOS induction in Escherichia coli PQ37. These genotoxicity spectra in bacteria are completely different from those observed with the bay-region diol-epoxides of chrysene and 3-hydroxychrysene. In V79 cells, the reverse diol-epoxides formed low levels of DNA adducts and were very weak inducers of gene mutations. In M2 mouse prostate cells, however, high numbers of transformed foci were induced by chrysene-3,4-diol and its diastereomeric 1,2-oxides. Chrysene-3,4-diol was somewhat more potent than chrysene-1,2-diol. The potency of both reverse diol-epoxides was similar to that of the syn-diastereomers of the bay-region diol-epoxides of chrysene and 3-hydroxychrysene, but lower than that of their anti-diastereomers. The reverse diol-epoxides of chrysene, unlike the bay-region diol-epoxides, were inactivated by purified microsomal epoxide hydrolase. Noteworthy findings were also made with regard to the chemical stability of the diol-epoxides in buffer, determined from the decline in mutagenicity after preincubation in the absence of the target cells. Despite its lower ΔEdeloc/β value for the formation of the benzylic carbocation, anti-chrysene-3,4-diol 1,2-oxide was shorter-lived (t½ = 46 min) than anti-chrysene-l,2-diol 3,4-oxide (t½ = 74 min). Unlike other investigated diastereomeric pairs of diol-epoxides, it was also shorter-lived than its syn-diastereomer (t½12 = 340 min
Improving dietary glucosinolate production, processing and characterization of potential health effects for the prevention of colon cancer
Der Wunderbaum Moringa oleifera – Ideale Quelle für aromatische Glucosinolate mit antikanzerogenem Potential
Renal organic anion transporters OAT1 and OAT3 mediate the cellular accumulation of 5-sulfooxymethylfurfural, a reactive, nephrotoxic metabolite of the Maillard product 5-hydroxymethylfurfural
Comparison of murine and human estrogen sulfotransferase inhibition in vitro and in silico—Implications for differences in activity, subunit dimerization and substrate inhibition
Sulfotransferase Forms Expressed in Human Intestinal Caco-2 and TC7 Cells at Varying Stages of Differentiation and Role in Benzo[ a
The presence of KCl in the exposure medium strongly influences the mutagenicity of metabolites of polycyclic aromatic hydrocarbons in Escherichia coli
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