Alterations in tumor biomarker GSTP gene methylation patterns induced by prenatal exposure to PFOS.
The adverse environmental exposure in early life may have adverse effects on animals through epigenetic aspects. The current study examined the possibility of early epigenetic alteration in PFOS-exposed rat liver. Pregnant Sprague-Dawley (SD) rats were exposed to perfluorooctane sulfonate (PFOS) at doses of 0.1, 0.6 and 2.0 mg/kg/d and 0.05% Tween 80 as control by gavage from gestation days 2 to 21. The dams were allowed to give birth and liver samples from weaned (postnatal day 21) offspring rats were analyzed for PFOS content, relative liver weight, global DNA methylation, methylation of LINE-1 regulatory region, tumor suppressor gene glutathione S-transferase pi (GSTP) and p16 promoter methylation level, as well as related genes expression level. In PFOS-exposed weaned rats, compared to the control, global DNA methylation and methylation of LINE-1 regulatory region decreased significantly only in the 2.0 mg/kg/d group. Up to 30% of critical CpG sites (+79, 81 and 84) in GSTP promoter region were methylated in the livers of PFOS-treated rats, while p16 promoter methylation was not affected. In addition, the up-regulated expression of GSTP was observed and this increase was associated with its main pathway of transcription regulation: Keap1-Nrf2/MafK. Thus, early-induced changes in critical cytosines within the GSTP gene promoter region may be a biomarker of hepatic PFOS burden, though their direct role in PFOS-induced hepatotoxicity, including its potential carcinogenic action, needs further research.
Wan
Yan-jian
YJ
Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, China.
Li
Yuan-yuan
YY
Xia
Wei
W
Chen
Jun
J
Lv
Zi-quan
ZQ
Zeng
Huai-cai
HC
Zhang
Ling
L
Yang
Wen-jie
WJ
Chen
Tian
T
Lin
Yi
Y
Wei
Jie
J
Xu
Shun-qing
SQ
D017738:Alkanesulfonic Acids / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002273:Carcinogens / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity; D019175:DNA Methylation; D015226:Dinucleoside Phosphates; D005260:Female; D005466:Fluorocarbons / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity*; D015870:Gene Expression; D005796:Genes; D051549:Glutathione S-Transferase pi / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism* / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012907:Smoking; D013723:Teratogens / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity*; D013792:Thalidomide / Q000378:metabolism / Q000494:pharmacology
D017738:Alkanesulfonic Acids; D015415:Biomarkers; D002273:Carcinogens; D015226:Dinucleoside Phosphates; D005466:Fluorocarbons; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D013723:Teratogens; D013792:Thalidomide; C015772:CpG dinucleotide; C076994:perfluorooctane sulfonic acid