Polychlorinated Biphenyls Induce Oxidative DNA Adducts in Female Sprague-Dawley Rats

被引:10
|
作者
Mutlu, Esra [1 ]
Gao, Lina [2 ]
Collins, Leonard B. [2 ]
Walker, Nigel J. [1 ]
Hartwell, Hadley J. [2 ]
Olson, James R. [3 ]
Sun, Wei [4 ]
Gold, Avram [2 ]
Ball, Louise M. [2 ]
Swenberg, James A. [2 ,5 ]
机构
[1] NIEHS, Natl Toxicol Program, NIH, POB 12233, Res Triangle Pk, NC 27709 USA
[2] Univ North Carolina Chapel Hill, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA
[3] SUNY Buffalo, Dept Pharmacol & Toxicol, Buffalo, NY 14214 USA
[4] Univ North Carolina Chapel Hill, Dept Biostat, Chapel Hill, NC 27599 USA
[5] Univ North Carolina Chapel Hill, Dept Environm Sci & Engn, Gillings Sch Global Publ Hlth, Campus Box 7431, Chapel Hill, NC 27599 USA
关键词
HEPATIC LIPID-PEROXIDATION; OXYGEN SPECIES PRODUCTION; TOXIC EQUIVALENCY FACTORS; CEREBELLAR GRANULE CELLS; MEMBRANE-BOUND ATPASES; PROTECTIVE ROLE; IN-VIVO; CHEMICAL CARCINOGENESIS; SUBCHRONIC EXPOSURE; CYTOCHROME-P450; 1A;
D O I
10.1021/acs.chemrestox.6b00146
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Polychlorinated biphenyls (PCBs) are organic chemicals that were traditionally produced and widely used in industry as mixtures and are presently formed as byproducts of pigment and dye manufacturing. They are known to persist and bioaccumulate in the environment. Some have been shown to induce liver cancer in rodents. Although the mechanism of the toxicity of PCBs is unknown, it has been shown that they increase oxidative stress, including lipid peroxidation. We hypothesized that oxidative stress-induced DNA damage could be a contributor for PCB carcinogenesis and analyzed several DNA adducts in female Sprague Dawley rats exposed to 3,3',4,4',5-pentachlorobiphenyl (PCB 126), 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153), and a binary mixture (PCB 126 + 153) for 14, 31, and 53 wks. Eight adducts were measured to profile oxidative DNA lesions, including 8-oxo-deoxyguanosine (8-oxo-dG), 1,N-6-ethenodeoxyadenosine (1,N-6-epsilon dA), N-2,3-ethenoguanine (N-2,3-epsilon G), 1,N-2-ethenodeoxyguanosine (1,N-2-epsilon dG), as well as malondialdehyde (M(1)dG), acrolein (AcrdG), crotonaldehyde (CrdG), and 4-nydroxynonenal-derived dG adducts (HNEdG) by LC-MS/MS analysis. Statistically significant increases were observed for 8-oxo-dG. and 1,N-6-epsilon dA. concentrations in hepatic DNA of female rats exposed to the binary mixture (1000 ng/kg/day + 1000 mu g/kg/day) but not in rats exposed to PCB 126 (1000 ng/kg/day) or PCB 153 (1000 mu g/kg/day) for 14 and 31 wks. However, exposure to PCB 126 (1000 ng/kg/day) for 53 wks significantly increased 8-oxo-dG, 1,N-6-epsilon dA, AcrdG, and M1dG. Exposure to PCB 153 (1000 mu g/kg/day) for 53 wks increased 8-oxo-dG, and 1,N-6-epsilon dA. Exposure to the binary mixture for 53 wks increased 8-oxo-dG, 1,N-6-epsilon dA., AcrdG, 1,N-2-epsilon dG, and N-2,3-epsilon G significantly above control groups. Increased hepatic oxidative DNA adducts following exposure to PCB 126, PCB 153; or the binary mixture shows that an increase in DNA damage may play an important role in hepatic toxicity and carcinogenesis in female Sprague Dawley rats.
引用
收藏
页码:1335 / 1344
页数:10
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