p53 gene expression is modulated by endocrine disrupting chemicals in the hermaphroditic fish, Kryptolebias marmoratus.
The full-length of cDNA of tumour suppressor gene p53 from the self-fertilizing fish Kryptolebias marmoratus (Km-p53) was determined using molecular cloning and rapid amplification of cDNA ends (RACE). The Complete cDNA sequences of K. marmoratus (Km-p53) gene was 1.8 kb in length. K. marmoratus p53 amino acid sequence showed a high degree of homology with the sequences from fishes, amphibians, and mammals. Although basal level of expression of Km-p53 mRNA was low, all the studied tissues showed some level of expression. After exposure of K. marmoratus to endocrine disrupting chemicals (EDCs) such as bisphenol A, 4-nonylphenol, and 4-tert-octylphenol, Km-p53 expression was significantly increased within 3 h of exposure in juveniles. However, expression was down-regulated by exposure to most of the EDCs when measured at 96 h in adult fish. In adult fish, suppressive effect of EDCs was more pronounced in liver as compared to other tissues. These findings suggest that Km-p53 gene would be involved in cellular defense mechanism in early stage of exposure to EDCs and long-term exposure may suppress its expression. It may be possible that the suppression of p53 by EDCs may predispose the host to environmental chemical carcinogenesis.
Lee
Young-Mi
YM
Department of Chemistry, and the National Research Lab of Marine Molecular and Environmental Bioscience, College of Natural Sciences, Hanyang University, Seoul 133-791, South Korea.
Rhee
Jae-Sung
JS
Hwang
Dae-Sik
DS
Kim
Il-Chan
IC
Raisuddin
Sheikh
S
Lee
Jae-Seong
JS
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001559:Benzhydryl Compounds; D003001:Cloning, Molecular; D015536:Down-Regulation; D052244:Endocrine Disruptors / Q000633:toxicity*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D016158:Genes, p53; D057850:Hermaphroditic Organisms; D007695:Killifishes / Q000235:genetics* / Q000254:growth & development; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D010636:Phenols / Q000633:toxicity; D010802:Phylogeny; D012333:RNA, Messenger / Q000378:metabolism; D017422:Sequence Analysis, DNA; D019849:Sex Determination Processes; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D010636:Phenols; D012333:RNA, Messenger; D014874:Water Pollutants, Chemical; C041594:4-nonylphenol; C105260:4-tert-octylphenol; C006780:bisphenol A; D000098826:Bisphenol A Compounds