Molecular-epidemiological studies on the risk evaluation of cancer induced by environmental carcinogen

环境致癌物致癌风险评估的分子流行病学研究

• 批准号: 12470086
• 负责人: TOMOKUNI Katsumaro
• 金额: $ 9.09万
• 依托单位: 佐賀医科大学
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12470086/
• 关键词: polycyclic aromatic hydrocarbons; cancer risk; DNA damage; DNA adducts; 8-oxodG; drug-metabolizing enzymes; polymorphism; 多環芳香族炭化水素暴露; 薬物代謝酵素遺伝子多型; 8-ヒドロキシデオキシグアノシン; コークス炉作業者; 分子疫学研究

This study was performed to evaluate the risk of cancer induced by environmental carcinogens such as polycyclic aromatic hydrocarbons (PAH) which are contained in the automobile exhaust and the cigarette smoke. We selected both heavy smokers and coke-oven workers in an iron-steel factory as the PAH-exposed human populations. A small quantity of peripheral blood and spot urine was collected from these subjects. The level of exposure to PAH was estimated by determining urinary 1-hydroxypyrene (1-OHP) which is urinary metabolite of PAH. We measured DNA adducts levels in lymphocytes or total white blood cells using 32P-postlabeling method. The level of DNA adducts had a significant positive correlation with the level of exposure to PAH. In addition, the level of DNA adducts was influenced by genetic polymorphism of metabolising enzyme, CYP1A1, suggesting that the adduct level was higher in mutant type than in wild type of CYP1A1 polymorphism. On the other hand, no significant correlation was found between the level of exposure to PAH and the level of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) levels which is useful as a biomarker of oxidative DNA damage.In conclusion, the measurement of DNA adducts in lymphocytes and/or white blood cells may be useful for estimating the DNA damage induced by PAH exposure, and for evaluating an environmental cancer risk.

本研究旨在评估汽车尾气和香烟烟雾中含有的环境致癌物质，如多环芳烃(PAH)的致癌风险。我们选择了一家钢铁厂的重度吸烟者和焦炉工人作为接触多环芳烃的人群。从这些受试者身上采集了少量的外周血液和点状尿液。通过测定尿液中多环芳烃的代谢物1-羟基苯(1-OHP)来评估接触多环芳烃的水平。用~(32)P-后标记法测定淋巴细胞或总白细胞的DNA加合物水平。DNA加合物水平与PAH暴露水平呈显著正相关。此外，代谢酶CYP1A1的遗传多态对DNA加合物的水平也有影响，表明突变类型的加合物水平高于野生型。另一方面，接触多环芳烃的水平与8-氧代-7，8-二氢-2‘-脱氧鸟苷(8-oxodG)水平之间没有明显的相关性，8-氧代-7，8-二氢-2’-脱氧鸟苷(8-oxodG)水平可作为DNA氧化损伤的生物标志物。

项目成果

J.Zhang: "Urinary 1-hydroxypyrene in coke oven workers relative to exposure, Alcohol consumption and metabolic enzymes"Occup Environ Med. 58. 716-721 (2001)

J.Zhang：“焦炉工人尿液中1-羟基芘与暴露、酒精消耗和代谢酶的关系”Occup Environ Med。

J.Zhang: "Aromatic DNA adducts in coke-oven workers, in relation to exposure, lifestyle and genetic……"International Archives of Occupational and Environmental Health. 73. 127-135 (2000)

J. 张：“焦炉工人中的芳香族 DNA 加合物，与暴露、生活方式和遗传有关……”国际职业和环境健康档案 73. 127-135 (2000)。

M.Ichiba: "Lymphocyte DNA adducts and polymorphism in the DNA repair enzyme XPD"Biomarkers. 6. 289-293 (2001)

M.Ichiba：“淋巴细胞 DNA 加合物和 DNA 修复酶 XPD 中的多态性”生物标记。

J.Zhang: "Aromatic DNA adducts in coke-oven workers, in relation to exposure, Lifestyle and genetic nolymorphism of metabolic enzymes"Int Arch Occup Environ Health. 73. 127-135 (2000)

J.Zhang：“焦炉工人中的芳香族 DNA 加合物与暴露、生活方式和代谢酶的遗传异型性的关系”Int Arch Occup Environ Health。

J.Zhang: "The relationship between arylhydrocarbon hydroxylase activity and DNA adducts measured by 32P-postlabelling assay in lymphocytes of lung cancer"Biomarkers. 5. 152-157 (2000)

J.Zhang：“通过 32P 标记后测定肺癌淋巴细胞中芳基烃羟化酶活性与 DNA 加合物之间的关系”生物标志物。