Organ-specific distribution of 7-chlorinated benz[a]anthracene and regulation of selected cytochrome P450 genes in rats

• Published in: Journal of toxicological sciences 2013/02/01, Vol.38(1), pp.137-143
• Main Authors: Sakakibara, Hiroyuki, Ohura, Takashi, Kido, Taketoshi, Yamanaka, Noriko, Tanimura, Nobuhiko, Shimoi, Kayoko, Guruge, Keerthi S.
• Format: Article
• Language: English
• Subjects: 7-Chlorinated benz[a]anthracene; Animals; Anthracenes - pharmacology; Benz(a)Anthracenes - blood; Benz(a)Anthracenes - pharmacology; Carcinogens - pharmacology; Chlorinated polycyclic aromatic hydrocarbons; Cytochrome P-450 Enzyme System - genetics; Cytochrome P450 enzymes; Environmental Pollutants - blood; Environmental Pollutants - pharmacology; Gene Expression Regulation, Enzymologic - drug effects; Kidney - metabolism; Liver - metabolism; Lung - metabolism; Male; Muscle, Skeletal - metabolism; Myocardium - metabolism; Organ-specific distribution; Rat; Rats; Rats, Inbred F344; Spleen - metabolism; Tissue Distribution
• ISSN: 0388-1350; 1880-3989
• DOI: 10.2131/jts.38.137

We previously reported that 14-day exposure to 7-chlorinated benz[a]anthracene (7-Cl-BaA), a new environmental pollutant, selectively induced hepatic cytochrome P450 (CYP)1A2 in rats, although treatment with its parent, benz[a]anthracene (BaA), induced CYP1A1, CYP1A2, and CYP1B1. In this study, to better understand the relative contribution of chlorination to the toxicity of polycyclic aromatic hydrocarbons (PAHs), we investigated the organ-specific distributions of 7-Cl-BaA and BaA in F334 rats. After 14 days of oral administration of 7-Cl-BaA or BaA at a concentration of 1 or 10 mg/kg body weight/day, both chemicals were detected in their plasma, which was collected 24 hr after the last administration, even at the lower dosage. Dose-dependent accumulation patterns were observed in the liver, muscle, kidney, spleen, heart, and lung. The 7-Cl-BaA concentrations in the organs were higher than those of the BaA. Furthermore, at the end of the exposure, 7-Cl-BaA specifically regulated several CYP genes in the heart more so than in other organs, although these inductions were not significant in the BaA treatment. 7-Cl-BaA might also stimulate the metabolic pathways of chemicals other than AhR-mediated metabolism, which is specific to normal PAHs, because of the alterations of CYP2J4, CYP4B1, and CYP17A1 expression in rats. In conclusion, our results imply that the chlorination of PAHs may change their organ-specific distribution and consequently alter their toxicological impacts compared to their parent PAHs.