Detoxification of benzo[a]pyrene primarily depends on cytochrome P450, while bioactivation involves additional oxidoreductases including 5-lipoxygenase, cyclooxygenase, and aldo-keto reductase in the liver
机构：[1]Hongqiao International Institute of Medicine, Shanghai Tong Ren Hospital and Faculty of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People’s Republic of China[2]Tong Ren Hospital Affiliated To Shanghai Jiao Tong University School of Medicine, Shanghai 200336, People’s Republic of China[3]KGPharma Limited, Foshan 528000, People’s Republic of China[4]Jiangsu Tripod Preclinical Research Laboratories, Pukou Economic Development Zone, Nanjing, People’s Republic of China[5]WadsworthCenter,New York StateDepartment of Health, Albany,NY12201-0509, USA
Cytochrome P450s are involved in detoxification and activation of benzo[a]pyrene (BaP) with unclear balance and unknown contribution of other oxidoreductases. Here, we investigated the BaP and BaP-induced mutagenicity in hepatic and extra-hepatic tissues using hepatic P450 reductase null (HRN) gpt mice. After 2-week treatment (50mg/kg, i.p. 4 days), BaP in the liver and lung of HRN-gpt mice were increased. BaP promoted gpt mutant frequency (MF) in HRN-gpt mice liver. MF of gpt in the lung and Pig-a in hematopoietic cells induced by BaP in HRN-gpt mice were increased than in gpt mice. BaP-7,8-diol-9,10-epoxide (BPDE)-DNA adducts in vitro was analyzed for enzymes detection in BaP bioactivation. Specific inhibitors of 5-lipoxygenase, cyclooxygenase-1&2, and aldo-keto reductase resulted in more than 80% inhibition rate in the DNA adduct formation, further confirmed by Macaca fascicularis hepatic S9 system. Our results suggested the detoxification of BaP primarily depends on cytochrome P450, while the bioactivation involves additional oxidoreductases.
基金：
National Natural Scientific
Foundation of China.Contact Grant Number: 21077112.
第一作者机构：[1]Hongqiao International Institute of Medicine, Shanghai Tong Ren Hospital and Faculty of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People’s Republic of China
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推荐引用方式(GB/T 7714)：
Wang Liupeng,Xu Wenwei,Ma Leilei,et al.Detoxification of benzo[a]pyrene primarily depends on cytochrome P450, while bioactivation involves additional oxidoreductases including 5-lipoxygenase, cyclooxygenase, and aldo-keto reductase in the liver[J].JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY.2017,31(7):doi:10.1002/jbt.21902.
APA：
Wang, Liupeng,Xu, Wenwei,Ma, Leilei,Zhang, Suxing,Zhang, Kezhi...&Luan, Yang.(2017).Detoxification of benzo[a]pyrene primarily depends on cytochrome P450, while bioactivation involves additional oxidoreductases including 5-lipoxygenase, cyclooxygenase, and aldo-keto reductase in the liver.JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY,31,(7)
MLA：
Wang, Liupeng,et al."Detoxification of benzo[a]pyrene primarily depends on cytochrome P450, while bioactivation involves additional oxidoreductases including 5-lipoxygenase, cyclooxygenase, and aldo-keto reductase in the liver".JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY 31..7(2017)
