Polycyclic aromatic hydrocarbons-induced ROS accumulation enhances mutagenic potential of T-antigen from human polyomavirus JC.
Polycyclic aromatic hydrocarbons-induced ROS accumulation enhances mutagenic potential of T-antigen from human polyomavirus JC.
复制标题
DOI：
10.1002/jcp.24375
复制
发表时间：
2013-11
影响因子：
5.6
通讯作者：
Reiss, Krzysztof
中科院分区：
文献类型：
--
作者：
Wilk, Anna;Waligorski, Piotr;Lassak, Adam;Vashistha, Himanshu;Lirette, David;Tate, David;Zea, Arnold H.;Koochekpour, Shahriar;Rodriguez, Paulo;Meggs, Leonard G.;Estrada, John J.;Ochoa, Augusto;Reiss, Krzysztof
Polycyclic aromatic hydrocarbons (PAHs) are the products of incomplete combustion of organic materials, which are present in cigarette smoke, deep-fried food, and in natural crude oil. Since PAH-metabolites form DNA adducts and cause oxidative DNA damage, we asked if these environmental carcinogens could affect transforming potential of the human Polyomavirus JC oncoprotein, T-antigen (JCV T-antigen). We extracted DMSO soluble PAHs from Deepwater Horizon oil spill in the Gulf of Mexico (oil-PAHs), and detected several carcinogenic PAHs. The oil-PAHs were tested in exponentially growing cultures of normal mouse fibroblasts (R508), and in R508 stably expressing JCV T-antigen (R508/T). The oil-PAHs were cytotoxic only at relatively high doses (1:50–1:100 dilution), and at 1:500 dilution the growth and cell survival rates were practically unaffected. This non-toxic dose triggered however, a significant accumulation of reactive oxygen species (ROS), caused oxidative DNA damage and the formation of DNA double strand breaks (DSBs). Although oil-PAHs induced similar levels of DNA damage in R508 and R508/T cells, only T-antigen expressing cells demonstrated inhibition of high fidelity DNA repair by homologous recombination (HRR). In contrast, low-fidelity repair by non-homologous end joining (NHEJ) was unaffected. This potential mutagenic shift between DNA repair mechanisms was accompanied by a significant increase in clonal growth of R508/T cells chronically exposed to low doses of the oil-PAHs. Our results indicate for the first time carcinogenic synergy in which oil-PAHs trigger oxidative DNA damage and JCV T-antigen compromises DNA repair fidelity.
登录
查看更多内容
DOI：
10.1073/pnas.96.20.11519
发表时间：
1999-09-28
影响因子：
11.1
作者：
Krynska, B;Del Valle, L;Khalili, K
通讯作者：
Khalili, K
影响因子：
2.8
作者：
Curfs, DMJ;Beckers, L;van Schooten, FJ
通讯作者：
van Schooten, FJ
DOI：
10.1016/j.ijheh.2009.12.005
发表时间：
2010-03-01
影响因子：
6
作者：
Liu, Hung-Hsin;Lin, Ming-Hsiu;Chen, Hsiu-Ling
通讯作者：
Chen, Hsiu-Ling
影响因子：
3.2
作者：
Del Valle, L;Wang, JY;Reiss, K
通讯作者：
Reiss, K
影响因子：
12.7
作者：
Del Valle, Luis;Khalili, Kamel
通讯作者：
Khalili, Kamel