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The induction of DNA adducts in mammalian cells exposed to 1-nitropyrene and its nitro-reduced derivatives

Edwards, Malcolm J., Batmanghelich, Shariar, Edwards, Stephen, Parry, James M. and Smith, Keith 1986. The induction of DNA adducts in mammalian cells exposed to 1-nitropyrene and its nitro-reduced derivatives. Mutagenesis 1 (5) , pp. 347-352.

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Abstract

1-Nitropyrene, 1-nitrosopyrene and 1-aminopyrene were investigated for their ability to induce covalently bound DNA adducts in calf thymus DNA and Chinese hamster lung fibroblasts. Xanthine oxidase catalysed the induction of one major and one minor DNA adduct in 1-nitropyrene- or 1-nitrosopyrene-treated calf thymus DNA, whilst 1-aminopyrene was inactive. These compounds did not form detectable DNA adducts in the absence of xanthine oxidase. The major DNA adduct produced by 1-nitropyrene and 1-nitrosopyrene in calf thymus DNA co-migrated on h.p.l.c., and the structure was consistent with that previously described by others as N-(deoxyguanosin-8-yl)-1-aminopyrene. The compounds were investigated for their ability to form DNA adducts in Chinese hamster lung fibroblasts. 1-Nitropyrene (5.2 pmol/mg DNA/h) and 1-nitrosopyrene (129 pmol/mg DNA/h) formed a single DNA adduct in Chinese hamster lung cells which co-eluted on h.p.l.c. with the C-8 deoxyguanosine adduct isolated from 1-nitropyrene-treated calf thymus DNA. 1-Nitrosopyrene was the most efficient compound investigated for the production of the C-8 guanine adducts. In contrast, 1-aminopyrene (14.7 pmol/mg DNA/h) induced the formation of a DNA adduct which did not co-elute with the C-8 guanine adduct. The data presented here suggest that 1-nitropyrene and 1-aminopyrene are metabolized to reactive intermediates which form different DNA adducts in Chinese hamster lung fibroblasts.

Item Type: Article
Status: Published
Schools: Chemistry
Subjects: Q Science > QD Chemistry
Publisher: Oxford University Press
ISSN: 0267-8357
Last Modified: 04 Jun 2017 02:57
URI: http://orca.cf.ac.uk/id/eprint/14543

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