title: Elevated tissue Cr levels, increased plasma oxidative markers, and global hypomethylation of blood DNA in male Sprague-Dawley rats exposed to potassium dichromate in drinking water.
abstract: Hexavalent chromium [Cr (VI)] is prevalent in ground water in some areas, but evidence on the toxic effects of Cr (VI) via ingestion through drinking water remains insufficient. The aims of our study were to investigate the toxic effects of Cr (VI) through oral water ingestion on oxidative stress and DNA methylation. Thirty-two Sprague-Dawley rats were randomly divided into four groups, and exposed to porassium dichromate (K2 Cr2 O7 ; 0, 30, 100, and 300 mg/L) in drinking water for 4 weeks. Mean body weight gain, mean water consumption, clinical chemistry determinations, and oxidative stress levels in plasma were measured. Global DNA methylation changes and DNA methylation status at the promoter of p16 gene were also detected. After 4 weeks, mild anemic effects and increased plasma malondialdehyde (MDA) levels occurred in rats exposed to 100 mg/L or 300 mg/L of Cr (VI). Plasma glutathione peroxidase (GSH-Px) activity decreased in all exposed groups. Global DNA methylation levels were reduced in 100 mg/L and 300 mg/L exposure groups. However, DNA methylation status at the promoter of P16 gene remained unchanged in all K2 Cr2 O7- treated groups. The correlation analysis indicated that increased MDA levels were closely correlated to global DNA hypomethylation. Our results indicated that oral ingestion of Cr (VI) through drinking water caused not only oxidative stress in plasma, but also global DNA hypomethylation in blood cells from male rats, and a good correlation was found between increased MDA levels and reduced global DNA methylation. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1080-1090, 2016.
authors.affiliation: Institute of Occupational Disease, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang, People's Republic of China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Eye Center, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; and Zhejiang Provincial Key Lab of Ophthalmology, Hangzhou, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.affiliation: Institute of Occupational Disease, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang, People's Republic of China.
authors.forename: Chunji
authors.initials: C
authors.lastname: Yao
authors.affiliation: Institute of Occupational Disease, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang, People's Republic of China.
authors.forename: Jianlin
authors.initials: J
authors.lastname: Lou
authors.affiliation: Institute of Occupational Disease, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang, People's Republic of China.
authors.forename: Riping
authors.initials: R
authors.lastname: Chen
authors.affiliation: Institute of Occupational Disease, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang, People's Republic of China.
authors.forename: Lingzhi
authors.initials: L
authors.lastname: Jin
authors.affiliation: Institute of Occupational Disease, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang, People's Republic of China.
authors.forename: Nanxiang
authors.initials: N
authors.lastname: Wu
authors.affiliation: Institute of Occupational Disease, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang, People's Republic of China.
authors.forename: Ming
authors.initials: M
authors.lastname: Gao
authors.affiliation: Institute of Occupational Disease, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang, People's Republic of China.
authors.forename: Peng
authors.initials: P
authors.lastname: Song
authors.affiliation: Institute of Occupational Disease, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang, People's Republic of China.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Tan
authors.affiliation: Institute of Occupational Disease, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang, People's Republic of China.
authors.forename: Kecheng
authors.initials: K
authors.lastname: Liu
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000284:Administration, Oral; D000818:Animals; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000097:blood; D019175:DNA Methylation / Q000187:drug effects*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis; D060766:Drinking Water / Q000737:chemistry*; D005260:Female; D005979:Glutathione Peroxidase / Q000097:blood; D007668:Kidney / Q000737:chemistry / Q000473:pathology; D008099:Liver / Q000737:chemistry / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects; D011192:Potassium Dichromate / Q000633:toxicity*; D011401:Promoter Regions, Genetic; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D060766:Drinking Water; D008315:Malondialdehyde; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D005979:Glutathione Peroxidase; D003849:Deoxyguanosine; D011192:Potassium Dichromate
keywords: DNA methylation; drinking water; hexavalent chromium; oxidative stress