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Hesse, S. ; Jernström, B. ; Martínez, M.A. ; Moldéus, P.W.* ; Christodoulides, L.G.* ; Ketterer, B.*

Inactivation of DNA-binding metabolites of benzo[a]pyrene and benzo[a]pyrene-7,8-dihydrodiol by glutathione and glutathione S-transferases.

Carcinogenesis 3, 757-761 (1982)
DOI
Open Access Green as soon as Postprint is submitted to ZB.
The binding to DNA of reactive metabolites of trans-7,8-dihydro-7,8-dihydroxybenzo[a]pyrene (BP-7,8-diol) was studied following the incubation of tritiated benzo[a]pyrene (BP) and BP-7,8-diol with nuclei from livers of 3-methylcholanthrene-treated rats. Binding was inhibited to a small extent by glutathione (GSH) alone and to a much greater extent by GSH and cytosol or purified GSH-transferase B and E. In this respect GSH-transferases A and C were also active, but less so. Inhibition of binding of BP-7.8-diol metabolites to DNA mediated by GSH-transferase was associated with the formation of GSH conjugates. The extent of inhibition of binding was similar in incubations of nuclei alone, nuclei and rat liver microsomes, and calf thymus DNA and rat liver microsomes. This indicates that reactive metabolites of BP-7,8-diol, formed either by nuclei or microsomes, are readily accessible to soluble GSH-transferases. GSH and cytosol were also active in inhibiting DNA-binding of reactive metabolites from 9-hydroxybenzo[a]pyrene (9-OH-BP). Thus, in the rat hepatocyte GSH and GSH-transferases may be important in protecting DNA from electrophilic attack by reactive BP-7.8-diol and 9-OH-BP species.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
ISSN (print) / ISBN 0143-3334
e-ISSN 1460-2180
Journal Carcinogenesis
Quellenangaben Volume: 3, Issue: 7, Pages: 757-761 Article Number: , Supplement: ,
Publisher Oxford University Press
Non-patent literature Publications
Reviewing status Peer reviewed