| Co-Investigator(Kenkyū-buntansha) |
NAGAYA Takashi Daiichi Shinseikai Hospital, Internal Med., The Head physician, 内科, 医長 (80262913)
KANBE Fukushi Nagoya Univ., Res. Inst. Environ. Med., Associate Professor, 環境医学研究所, 助教授 (00211871)
SEO Hisao Nagoya Univ., Res. Inst. Environ. Med., Professor, 環境医学研究所, 教授 (40135380)
YAMAMOTO Ryuhei Kurabo Industries LTD., Technical Reasearch Laboratory, Biochemical Dept., Chief Researcher, 技術研究所, 主任研究員
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| Research Abstract |
2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin (TCDD) and related halogenated aromatic hydrocarbons are potential environmental contaminants that have a pleiotropic adverse biological effects on living animals. Exposure to TCDD leads to tumor promotion, teratogenesis, immunosuppression, hepatotoxicity, and reproductive toxicity etc. The effects of TCDD are believed to be mediated by aryl hydrocarbon receptor (AhR) that is a ligand-activated transcription factor. Most of the TCDD-responsive genes identified to date code for enzymes associated with various metabolic pathways within the liver. However, considering the divergent biological effects of TCDD like teratogenesis and tumor promotion, genes associated with cell division, cell cycle regulation or cell adhesion are likely ao be regulated by TCDD. We, therefore, employed CDNA representational difference analysis to identify new genes that are upregulated by 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) in a human hepatoblastoma cell line HepG2. We isolated several TCDD-responsive cDNAs. Sequence analysis revealed that one of them encodes E16/ CD98LC/ hLATl, an integral membrane protein involved in multiple cellular functions including cellular transport of L-type amino acids. Northern blot analysis confirmed the TCDD-dependent upregulation of the mRNA. Induction of E16/ CD98LC/ hLATl mRNA by TCDD did not require de novo protein synthesis as revealed by the experiment using cycloheximide. Consistent with the changes at mRNA level, the transport of 3H-leucine into HepG2 cells was significantly increased by TCDD treatment. These findings provide a novel aspect of biological effects of TCDD on human hepatocytes.
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