Health effect and molecular markers in humans exposed to dioxin-like chemicals

• Main Authors: Pei-Chien Tsai, 蔡佩倩
• Other Authors: Yueliang Leon Guo
• Format: Others
• Language: zh-TW
• Published: 2008
• Online Access: http://ndltd.ncl.edu.tw/handle/91014044454661721901

博士 === 國立成功大學 === 基礎醫學研究所 === 96 === Dioxin-like chemicals include polychlorodibenzodioxin (PCDD), polychlorinated biphenyls (PCBs), and polychlorinated dibenzofurans (PCDFs). Toxicity of them has been broadly reported in animal studies. However, the health effect and molecular markers in human exposed to dioxin-like chemicals were still unclear. Therefore, a group of Yucheng cases in central Taiwan ingested cooking oil contaminated with PCBs/PCDFs have followed. Gene suscepbility, potential exposure markers, and early effect markers were studied for evaluating the relationship between exposure and diseases. In this thesis, we followed up a group of people highly exposed to PCBs and PCDFs, and examined: (1) the difference in long term mortality between exposed group and background population; (2) whether genetic polymorphisms of AhR, CYP1A1 and GST affected susceptibility for developing skin manifestations in exposed people; and (3) potential exposure molecular markers for such exposure. The overall and cause-specific mortality of the exposed group were compared to those of the Taiwan general population. An age-modified method was to calculate standardized mortality ratio (SMR). Between 0-8 years after exposure, mortality of chronic liver disease and cirrhoses was increased in the Yucheng men, but not in women. Between 8-24 years after the exposure, mortality of systemic lupus erythematosus (SLE) was increased significantly in Yucheng females (five deaths, SMR = 14.7) Questionnaires with telephone interview were used to obtain occurrence of skin manifestations in Yucheng groups. Polymerase chain reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP) was done for determination of gentic polymorphism. Among intermediately exposed individuals, GSTM1 null genotype was associated with skin allergy. Among highly exposed individuals, combined CYP1A1-MspI mutant genotype and GSTM1 null genotype were associated with increased risk of chloracne. A cDNA microarray system consisted of 908 genes was used for pooled mRNA among non-smoking men exposed to PCBs/PCDFs and their reference in triplicates. After adjusting for background and housekeeping genes, genes with different expressions between exposure and reference groups were determined by both regression and cluster analysis, and further confirmed by real-time PCR. Von Hippel Lindau (VHL) was found reduced in Yucheng people by both methods, after adjusted for age. Among Yucheng people, those with abnormal nails had lower VHL expression than those without abnormal nails. As new health outcomes were found among people highly exposed to PCBs/PCDFs, and genetic susceptibility and exposure markers were identified in this study, we believe further follow-up of these people is important. Further investigation on cancer mortality, mechanism of autoimmune diseases, and other biomarkers are warranted.