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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
Author(s) -
Wang Liupeng,
Xu Wenwei,
Ma Leilei,
Zhang Suxing,
Zhang Kezhi,
Ye Peizhen,
Xing Guozhen,
Zhang Xuefeng,
Cao Yiyi,
Xi Jing,
Gu Jun,
Luan Yang
Publication year - 2017
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.21902
Subject(s) - chemistry , benzo(a)pyrene , reductase , cytochrome p450 , biochemistry , epoxide hydrolase , enzyme , detoxification (alternative medicine) , cytochrome , carcinogen , microsome , microbiology and biotechnology , biology , medicine , alternative medicine , pathology
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 (50 mg/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.