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Effects of mixing metal ions on oxidative DNA damage mediated by a Fenton-type reduction.
Identification of the major tamoxifen-deoxyguanosine adduct formed in the liver DNA of rats treated with tamoxifen.
The antiestrogenic drug tamoxifen induces liver tumors in rats by a genotoxic mechanism. The key step has been proposed to be the formation of a reactive carbocation from the metabolite
Mutation in mammalian cells by stereoisomers of anti-benzo[a] pyrene-diolepoxide in relation to the extent and nature of the DNA reaction products.
It is proposed that mutagenicity in V79 cells, which correlates closely with reported carcinogenicity data in mice, is a consequence of reaction with DNA at the amino-group of guanine and that the difference found between the (+) and (-) stereoisomers results from differences in the spatial orientation of the benzo[a]pyrene residue at this site.
Environmental pollutant and potent mutagen 3-nitrobenzanthrone forms DNA adducts after reduction by NAD(P)H:quinone oxidoreductase and conjugation by acetyltransferases and sulfotransferases in human
The role of human hepatic NQO1 is shown to reduce 3- NBA to species being further activated by NATs and SULTs, indicating that 3-NBA is predominantly activated by cytosolic nitroreductases rather than microsomal POR.
N-demethylation accompanies alpha-hydroxylation in the metabolic activation of tamoxifen in rat liver cells.
It is demonstrated that in rat liver cells in vivo and in vitro, Phase I metabolic activation of tamoxifen involves both alpha-hydroxylation and N-demethylation, which is followed by Phase II activation at the alpha-position to form a highly reactive sulphate.
Resolution of alpha-hydroxytamoxifen; R-isomer forms more DNA adducts in rat liver cells.
The genotoxic tamoxifen metabolite alpha-hydroxytamoxifen has been resolved into R- and S-enantiomers. This was achieved by preparing its ester with S-camphanic acid, chromatographic separation into
Minor products from the reaction of (+) and (-) benzo[a]-pyrene-anti-diolepoxide with DNA.
It was found that the O6 and 7-guanine products were derived mainly from reaction of the (-)isomer, and the 7-substituted guanine derivative in DNA was unstable, undergoing either spontaneous release of the substituted Guanine or imidazole ring opening.
Alkylation of DNA by the nitrogen mustard bis(2-chloroethyl)methylamine.
Four principal products ofkylation of DNA by the nitrogen mustard bis(2-chloroethyl)methylamine (mechlorethamine; HN2) gave four principal products, derived by mono-alkylation of guanine at N-7 and adenine atN-3 and by cross-linking of Guanine to guaninea or guanines to adenines at these positions.