title: Polychlorinated Biphenyls Induce Oxidative DNA Adducts in Female Sprague-Dawley Rats.
abstract: 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)-εdA), N(2),3-ethenoguanine (N(2),3-εG), 1,N(2)-ethenodeoxyguanosine (1,N(2)-εdG), as well as malondialdehyde (M1dG), acrolein (AcrdG), crotonaldehyde (CrdG), and 4-hydroxynonenal-derived dG adducts (HNEdG) by LC-MS/MS analysis. Statistically significant increases were observed for 8-oxo-dG and 1,N(6)-εdA concentrations in hepatic DNA of female rats exposed to the binary mixture (1000 ng/kg/day + 1000 μg/kg/day) but not in rats exposed to PCB 126 (1000 ng/kg/day) or PCB 153 (1000 μg/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)-εdA, AcrdG, and M1dG. Exposure to PCB 153 (1000 μg/kg/day) for 53 wks increased 8-oxo-dG, and 1,N(6)-εdA. Exposure to the binary mixture for 53 wks increased 8-oxo-dG, 1,N(6)-εdA, AcrdG, 1,N(2)-εdG, and N(2),3-εG 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.
authors.affiliation: National Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, United States.
authors.forename: Esra
authors.initials: E
authors.lastname: Mutlu
authors.affiliation: Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
authors.forename: Lina
authors.initials: L
authors.lastname: Gao
authors.affiliation: Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
authors.forename: Leonard B
authors.initials: LB
authors.lastname: Collins
authors.affiliation: National Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, United States.
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Walker
authors.affiliation: Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
authors.forename: Hadley J
authors.initials: HJ
authors.lastname: Hartwell
authors.affiliation: Department of Pharmacology and Toxicology, State University of New York at Buffalo, Buffalo, New York 14214, United States.
authors.forename: James R
authors.initials: JR
authors.lastname: Olson
authors.affiliation: Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
authors.affiliation: Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
authors.forename: Avram
authors.initials: A
authors.lastname: Gold
authors.affiliation: Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
authors.forename: Louise M
authors.initials: LM
authors.lastname: Ball
authors.affiliation: Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
authors.forename: James A
authors.initials: JA
authors.lastname: Swenberg
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid; D018736:DNA Adducts / Q000378:metabolism*; D005260:Female; D018384:Oxidative Stress / Q000187:drug effects*; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry
chemical_list: D018736:DNA Adducts; D011078:Polychlorinated Biphenyls