Health & Environmental Research Online (HERO)


Print Feedback Export to File
1010848 
Journal Article 
Benzo[a]pyrene induces complex H2AX phosphorylation patterns by multiple kinases including ATM, ATR, and DNA-PK 
Yan, C; Lu, J; Zhang, G; Gan, T; Zeng, Q; Shao, Z; Duerksen-Hughes, PJ; Yang, J 
2011 
1 
Toxicology In Vitro
ISSN: 0887-2333
EISSN: 1879-3177 
25 
1 
91-99 
English 
20888899 
WOS:000287010600012 
H2AX is phosphorylated (γH2AX) by members of the phosphatidylinositol 3-kinase (PI3K) family, including ataxia telangiectasia-mutated (ATM), ATM- and Rad3-related (ATR) and DNA-PK in response to DNA damage. While it has been reported that benzo[a]pyrene (BaP) cannot induce γH2AX alone in several cell lines, we have shown that BaP alone could induce γH2AX in human amnion FL cells. Thus, we further examined the ability of BaP to induce γH2AX in different cell systems. It was shown that BaP-induced γH2AX in HeLa cells in a time- and dose-dependent manner. BaP also induced γH2AX in ATM(-/-) mouse fibroblasts, DNA-PKcs(-/-) mouse fibroblasts, and a genetically modified human osteosarcoma U2OS cell line. PI3K inhibitors caffeine and wortmannin were then used in an effort to identify the kinase(s) responsible for BaP-induced γH2AX. Unexpectedly, in BaP-treated HeLa cells, caffeine pretreatment did not inhibit but rather increased γH2AX level. On the other hand, caffeine or wortmannin can inhibit BaP-induced γH2AX in either U2OS, DNA-PKcs(-/-) or ATM(-/-) cells. Taken together, these data suggest that BaP alone can induce H2AX phosphorylation in certain cell systems, and that members of the PI3K family, including ATM, ATR, and DNA-PK can participate in the phosphorylation of H2AX in the various cell types. 
Benzo[a]pyrene; Caffeine; DNA damage; H2AX; Phosphatidylinositol 3-kinase 
IRIS
• Benzo(a)pyrene (BaP)
     Considered