Journal Article

Analysis of polychlorinated biphenyl-DNA adducts by <sup>32</sup>P-postlabeling

Greg G. Oakley, Larry W. Robertson and Ramesh C. Gupta

in Carcinogenesis

Volume 17, issue 1, pages 109-114
Published in print January 1996 | ISSN: 0143-3334
e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/17.1.109
Analysis of polychlorinated biphenyl-DNA adducts by 32P-postlabeling

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Previous studies reported that metabolic activation of certain polychlorinated biphenyls (PCBs) resulted in binding to protein, RNA and DNA fractions. However, the formation of DNA adducts has not been demonstrated nor have methods been optimized for the detection of such adducts. In the present study we investigated activation and binding to DNA of lower chlorinated biphenyls using 32P-postlabeling. The incubation of 2-chloro-, 3-chloro-, 3, 4-dichloro- and 3, 4, 5-trichlorobiphenyl with calf thymus DNA and liver microsomes from rats treated with pheno-barbital and 3-methylcholanthrene, followed by oxidation with a peroxidase, produced 1–3 major adducts. Reaction of deoxyguanosine 3'-monophosphate with metabolites of the congeneric chlorinated biphenyls produced adducts with similar chromatographic mobility as those with DNA, suggesting that guanine was the preferential site of attack. Furthermore butanol and nuclease P1 enrichments showed different adduct recoveries, depending upon the the chloro-biphenyl. Adducts derived from incubations with mono-chlorobiphenyls were recovered 2- to 3-fold higher with butanol, while the recovery of di- and tri-chlorobiphenyl adducts was 5- to 7-fold higher with nuclease P1. DNA adducts formed during the metabolism of 3, 4-dichlorobi-phenyl were reduced by the sulfur nucleophiles, glutathione and N-acetyl-L-cysteine, suggesting that reactive semiquin-one(s) or quinone(s) are involved. In contrast, the addition of superoxide dismutase increased adduct formation, suggesting that the quinone metabolites are responsible for the major adducts formed. Our results are consistent with the hypothesis that lower chlorinated biphenyls are metabolically activated to electrophilic quinoid species which bind to DNA.

Journal Article.  0 words. 

Subjects: Clinical Cytogenetics and Molecular Genetics

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