Modulatory effect of environmental endocrine disruptors on N- ras oncogene expression in the hermaphroditic fish, Kryptolebias marmoratus

• Published in: Comparative biochemistry and physiology. Toxicology & pharmacology Vol. 147; no. 3; pp. 299 - 305
• Main Authors: Lee, Young-Mi, Raisuddin, Sheikh, Rhee, Jae-Sung, Ki, Jang-Seu, Kim, Il-Chan, Lee, Jae-Seong
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2008
• Subjects: Amino Acid Sequence; Animals; Base Sequence; Benzhydryl Compounds; Carcinogenicity Tests; Cloning, Molecular; Endocrine disrupting chemicals; Endocrine Disruptors - toxicity; Environmental carcinogenesis; Environmental Monitoring - methods; Fish; Gene Expression - drug effects; Genes, ras; Hermaphroditic Organisms; Killifishes - genetics; Killifishes - growth & development; Kryptolebias marmoratus; Molecular Sequence Data; N- ras; Oncogenes; Phenols - toxicity; Phylogeny; Reverse Transcriptase Polymerase Chain Reaction; Sequence Analysis, DNA; Sex Determination Processes; Tissue Distribution; Up-Regulation; Water Pollutants, Chemical - toxicity; Kryptolebias marmoratus; Fish; Environmental carcinogenesis; Oncogenes; N- ras; Endocrine disrupting chemicals
• ISSN: 1532-0456; 1878-1659
• DOI: 10.1016/j.cbpc.2007.11.006

Kryptolebias marmoratus is the only known internally self-fertilizing vertebrate. It shows high susceptibility to many chemical carcinogens and has been proposed as a potential cancer model species alternative to mammals. Since use of this fish species is expected to rise in cancer research, regulation of oncogenes from K. marmoratus needs proper understanding. We cloned and deduced full-length sequence of cDNA of N- ras oncogene from K. marmoratus. Study of expression profile of N- ras by using quantitative real-time RT-PCR revealed that brain had the highest level of expression compared to other tissues. Some embryonic stages showed more N- ras expression than juveniles and adults. Exposure to two environmental endocrine disrupting chemicals (EDCs), bisphenol A (BPA) and 4-nonylphenyl (NP) caused up-regulation of N- ras in gonad, intestine and liver of hermaphrodite K. marmoratus. It is suggested that K. marmoratus may be a suitable model species for oncogene expression studies. The observed EDC-induced expression of N- ras supports the assumption that EDC exposure may predispose the host to the risk of environmental carcinogenesis.