Tumor formation in the neonatal mouse bioassay indicates that the potent carcinogen dibenzo[def,p]chrysene (dibenzo[a,l]pyrene) is activated in vivo via its trans-11,12-dihydrodiol

Chemico-biological Interactions
K L PlattAndreas Luch

Abstract

The hexacyclic aromatic hydrocarbon dibenzo[def,p]chrysene, better known as dibenzo[a,l]pyrene (DBP) in the field of chemical carcinogenesis, is present in the environment as a combustion product of organic matter. This compound is probably the strongest chemical carcinogen ever tested. As ultimate genotoxic metabolites of DBP two electrophilically reactive species are discussed: (i) radical cations generated by one-electron oxidation, and (ii) fjord region dihydrodiol epoxides formed via the trans-11,12-dihydroxy 11,12-dihydro derivative of DBP (11,12-dihydrodiol). In order to delineate the metabolic pathway(s) involved in tumor formation by DBP, newborn Crl:CD-1(ICR)BR mice were intraperitoneally treated with the parent compound, its 11,12-dihydrodiol, and the two diastereomeric fjord region dihydrodiol epoxides. Due to severe acute and chronic toxicity, the total dose of DBP and of the 11,12-dihydrodiol was limited to 40 nmol. For the same reason the dihydrodiol epoxides could only be applied in doses up to 0.4 nmol. The tumor incidence was determined 55 +/- 1 weeks after treatment. Under these conditions, DBP and its 11,12-dihydrodiol induced lung tumors (incidence: 86.5% versus 92.0%; yield: 2.88 versus 7.44 tumors per mou...Continue Reading

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Citations

Jun 8, 2013·Toxicological Sciences : an Official Journal of the Society of Toxicology·Susan Ritger CrowellRichard A Corley
Mar 1, 2013·Cancer Prevention Research·Abby D Benninghoff, David E Williams
Oct 18, 2011·Toxicology and Applied Pharmacology·Susan Ritger CrowellRichard A Corley
Jul 20, 2007·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Martin WikelskiEberhard Gwinner
Jun 11, 2010·Proceedings. Biological Sciences·Barbara Helm, Marcel E Visser
Jul 27, 2011·Journal of Environmental Monitoring : JEM·Shilong WeiJiamo Fu

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