Journal Article

Covalent DNA adducts formed in mouse epidermis by benzo(g)chrysene

A.S. Giles, A. Seidel and D.H. Phillips

in Carcinogenesis

Volume 17, issue 6, pages 1331-1336
Published in print June 1996 | ISSN: 0143-3334
Published online June 1996 | e-ISSN: 1460-2180 | DOI:
Covalent DNA adducts formed in mouse epidermis by

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The metabolic activation in mouse skin of benzo(g)chrysene (B(g)C), a moderately carcinogenic polycyclic aromatic hydrocarbon (PAH) present in coal tar, was investigated. Male Parkes mice were treated topically with 0.5 μmol B(g)C and DNA was isolated from the treated areas of skin at various times after treatment and analysed by 32P-post-labelling. Seven major adduct spots were detected, at a maximum level of 6.55 fmol adducts/μg DNA. Mouse skin treated with the PAH benzo(c)phenanthrene (B(c)Ph) gave a total of 0.24 fmol adducts/μg DNA. B(g)C-DNA adducts persisted in skin for at least 3 weeks. Treatment of mice with 0.5 μmol of the optically pure putative proximate carcinogens, the (+)- and (−)-trans benzo(g)chrysene-11, 12-dihydrodiols, led to the formation of adducts which co-migrated on TLC and HPLC with those formed in B(g)C-treatedmice, which suggested that the detected adducts were formed by the fjord region B(g)C-11, 12-dihydrodiol-13, 14-epoxides (B(g)CDEs). To test this, the four optically pure synthetic B(g)CDEs were reacted in vitro with DNA and the heteroco-polymers poly(dA.dT) and poly(dG-dC) and these samples 32P-postlabelled. Co-chromatography, onboth TLC and HPLC, of in vitro and in vivo adducts indicated that B(g)Cis activated in mouse skin through formation of the (−)-anti-(11R,12S, 13S,14R) and (+)-syn-(11S, 12R,13S,14R) B(g)CDEs. (−)-anti-B(g)CDE formed five adducts with DNA, two of them with adenine and three with guanine bases. (+)-syn-B(g)CDE formed one adduct with each of these bases in DNA. The adenine adducts accounted for 64% of the total major adducts formed in B(g)C-treated mouse skin. The route of metabolic activation of B(g)C is similar to that reported for B(c)Ph, but the extent of activation to the fjord region diol-epoxides is significantly greater in the case of B(g)C, as demonstrated by the higher levels of adduct formation in vivo.

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Subjects: Clinical Cytogenetics and Molecular Genetics

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