RETRACTED: Role of DNA methylation in cell cycle arrest induced by Cr (VI) in two cell lines.
Hexavalent chromium [Cr(IV)], a well-known industrial waste product and an environmental pollutant, is recognized as a human carcinogen. But its mechanisms of carcinogenicity remain unclear, and recent studies suggest that DNA methylation may play an important role in the carcinogenesis of Cr(IV). The aim of our study was to investigate the effects of Cr(IV) on cell cycle progress, global DNA methylation, and DNA methylation of p16 gene. A human B lymphoblastoid cell line and a human lung cell line A549 were exposed to 5-15 µM potassium dichromate or 1.25-5 µg/cm² lead chromate for 2-24 hours. Cell cycle was arrested at G₁ phase by both compounds in 24 hours exposure group, but global hypomethylation occurred earlier than cell cycle arrest, and the hypomethylation status maintained for more than 20 hours. The mRNA expression of p16 was significantly up-regulated by Cr(IV), especially by potassium dichromate, and the mRNA expression of cyclin-dependent kinases (CDK4 and CDK6) was significantly down-regulated. But protein expression analysis showed very little change of p16 gene. Both qualitative and quantitative results showed that DNA methylation status of p16 remained unchanged. Collectively, our data suggested that global hypomethylation was possibly responsible for Cr(IV)-induced G₁ phase arrest, but DNA methylation might not be related to up-regulation of p16 gene by Cr(IV).
Institute of Hygiene, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang, People's Republic of China. jianlinlou@163.com
Jianlin
J
Lou
Yu
Y
Wang
Chunji
C
Yao
Lingzhi
L
Jin
Xiuzhi
X
Wang
Yun
Y
Xiao
Nanxiang
N
Wu
Peng
P
Song
Yang
Y
Song
Yufeng
Y
Tan
Ming
M
Gao
Kecheng
K
Liu
Xing
X
Zhang
D002274:Carcinogens, Environmental / Q000633:toxicity*; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D059447:Cell Cycle Checkpoints / Q000187:drug effects* / Q000235:genetics*; D002460:Cell Line; D002857:Chromium / Q000633:toxicity*; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics / Q000378:metabolism; D051361:Cyclin-Dependent Kinase 6 / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects; D019942:Genes, p16 / Q000187:drug effects; D006801:Humans; D011401:Promoter Regions, Genetic / Q000187:drug effects; D012995:Solubility
D002274:Carcinogens, Environmental; D002857:Chromium; C074702:chromium hexavalent ion; C495911:CDK6 protein, human; D051358:Cyclin-Dependent Kinase 4; D051361:Cyclin-Dependent Kinase 6