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DOI10.1021/acs.chemrestox.6b00368
DNA Product Formation in Female Sprague-Dawley Rats Following Polyhalogenated Aromatic Hydrocarbon (PHAH) Exposure
Gao, Lina1; Mutlu, Esra3; Collins, Leonard B.1; Walker, Nigel J.3; Hartwell, Hadley J.1; Olson, James R.4; Sun, Wei2; Gold, Avram1; Ball, Louise M.1; Swenberg, James A.1
发表日期2017-03-01
ISSN0893-228X
卷号30期号:3页码:794-803
英文摘要

DNA oxidation damage has been regarded as one of the possible mechanisms for the hepatic carcinogenesis of dioxin-like compounds (DLCs). In this study, we evaluated the toxic equivalency factor (TEF) from the standpoint of induced DNA oxidation products and their relationship to toxicity and carcinogenicity. Nine DNA oxidation products were analyzed in the liver of female Sprague-Dawley rats exposed to 2,3,7,8tetrachlorodibenzo-pdioxin (TCDD) alone or the tertiary mixture of TCDD, 3,3',4,4',5-pentachlorobiphenyl (PCB 126), and 2,3,4,7,8-pentachlorodibenzofuran (PeCDF) by gavage for 14, 31, and 53 weeks (5 days/week) by LC-MS/MS: 8-oxo-7,8dihydro-2'-deoxyguanosine (8-oxo-dGuo); 1,N6-etheno-2'-deoxyadenosine (1,N6-edAdo); N2,3-ethenoguanine (N2,3-8G); 7-(2oxoethly)guanine (7-OEG); 1,N2-etheno-2'-deoxyguanosine (1,N2-edGuo); malondialdehyde (M1dGuo); acrolein (AcrdGuo); crotonaldehyde (CrdGuo); and 4-hydroxynonenal (HNEdGuo) derived 2'-deoxyguanosine adducts. Exposure to TCDD (100 ng/kg/day) significantly induced 1,N6-edAdo at 31 and 53 weeks, while no increase of 8-oxo-dGuo was observed. Significant increases were observed for 8-oxo-dGuo and 1,N6-edAdo at all time points following exposure to the tertiary mixture (TEQ100 ng/kg/day). Exposure to TCDD for 53 weeks only significantly increased 1,N6-edAdo, while increases of N2,3-eG and 7-OEG were only found in the highest dose group (100 ng/kg/day). Exposure to the tertiary mixture for 53 weeks had no effect on N2,3eG in any exposure group (TEQO, 22, 46, or 100 ng/kg/day), while significant increases were observed for 1,N6-edAdo (all dose groups), 8-oxo-dGuo (46 and 100 ng/kg/day), and 7-OEG (100 ng/kg/day). While no significant increase was observed at 53 weeks for 1,N2-epsilon dGuo, M1dGuo, AcrdGuo, or CrdGuo following exposure to TCDD (100 ng/kg/day), all of them were significantly induced in animals exposed to the tertiary mixture (TEQ100 ng/kg/day). This oxidation DNA product data suggest that the simple TEF methodology cannot be applied to evaluate the diverse patterns of toxic effects induced by DLCs.


语种英语
WOS记录号WOS:000397171300006
来源期刊CHEMICAL RESEARCH IN TOXICOLOGY
来源机构美国环保署
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/60505
作者单位1.Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA;
2.Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA;
3.NIH, Natl Inst Environm Hlth Sci, Natl Toxicol Program, RTP, Durham, NC 27709 USA;
4.SUNY Buffalo, Dept Pharmacol & Toxicol, Buffalo, NY 14214 USA
推荐引用方式
GB/T 7714
Gao, Lina,Mutlu, Esra,Collins, Leonard B.,et al. DNA Product Formation in Female Sprague-Dawley Rats Following Polyhalogenated Aromatic Hydrocarbon (PHAH) Exposure[J]. 美国环保署,2017,30(3):794-803.
APA Gao, Lina.,Mutlu, Esra.,Collins, Leonard B..,Walker, Nigel J..,Hartwell, Hadley J..,...&Swenberg, James A..(2017).DNA Product Formation in Female Sprague-Dawley Rats Following Polyhalogenated Aromatic Hydrocarbon (PHAH) Exposure.CHEMICAL RESEARCH IN TOXICOLOGY,30(3),794-803.
MLA Gao, Lina,et al."DNA Product Formation in Female Sprague-Dawley Rats Following Polyhalogenated Aromatic Hydrocarbon (PHAH) Exposure".CHEMICAL RESEARCH IN TOXICOLOGY 30.3(2017):794-803.
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