p53 gene expression is modulated by endocrine disrupting chemicals in the hermaphroditic fish, Kryptolebias...

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.