Fundamental Toxicological Sciences

Paper Details

Fundamental Toxicological Sciences
Vol. 1 No. 3 November 10, 2014 p.101-108
Original Article
Sex-dependent difference in the hepatic and pulmonary toxicological effects in mice administrated 7-chlorinated benz[a]anthracene
  • Takashi Ohura (Faculty of Agriculture, Meijo University / ohura@meijo-u.ac.jp)
  • Keerthi S. Guruge (Pathology and Pathophysiology Research Division, National Institute of Animal Health, National Agriculture and Food Research Organization / guruge@affrc.go.jp)
Hiroyuki Sakakibara 1) , Takashi Ohura 2) , Yuta Kamiya 2) , Noriko Yamanaka 3) , Nobuaki Shimada 3) , Kayoko Shimoi 4) , Keerthi S. Guruge 3)
1) Faculty of Agriculture, University of Miyazaki , 2) Faculty of Agriculture, Meijo University , 3) Pathology and Pathophysiology Research Division, National Institute of Animal Health, National Agriculture and Food Research Organization , 4) Graduate School of Integrated Pharmaceutical and Nutritional Sciences, University of Shizuoka
Keywords: 7-Chlorinated benz[a]anthracene, Chlorinated polycyclic aromatic hydrocarbons, Cytochrome P450 1 family, Mice, Gender difference
Abstracts

Chlorinated polycyclic aromatic hydrocarbons (Cl-PAHs) have recently been found in the environment at relatively high concentrations. However, their toxicological information has not been well documented. In this study, a 24 hr in vivo experiment was conducted to evaluate the sex-dependent difference of the acute toxicological effects of 7-chlorinated benz[a]anthracene (7-ClBaA) as a model Cl-PAH. 7-ClBaA or its parent chemical, BaA, was once orally administered to male or female ICR mice at concentrations of 1, 10, and 100 mg/kg body weight. The relative liver weights of the males were significantly increased at the highest dose of both chemicals compared to the vehicle controls, but the weights were comparable among all groups in the females. The plasma 7-ClBaA level was similar in both sexes, but significantly higher than that of BaA. 7-ClBaA dose-dependently induced expression of the genes Cyp1a1, 1a2, and 1b1 in the liver and lung, and these stimulations were significantly higher in both organs and genders at a dose of 100 mg/kg 7-ClBaA compared with an equivalent amount of BaA, except in the case of hepatic Cyp1a2 and 1b1 and pulmonary Cyp1a2 in the female mice. The results suggest that acute toxicity of 7-ClBaA is gender- and organ-specific, and female mice might be less sensitive to acute toxicity of both 7-ClBaA and BaA than the males.