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To Establish Cytometric Epidemiology by Measuring Benzo[a]pyrene-DNA Adducts as an Example

以苯并[a]芘-DNA 加合物的测定为例建立细胞流行病学

基本信息

批准号：
13670350
负责人：
INOUE Shoichi
金额：
$ 1.98万
依托单位：
HOKKAIDO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670350/
关键词：
BPDE-DNA adducts Peripheral lymphocytes Flow cytometry Air temperature Epidemiology Lung cancer Regional difference 5D11 antibody

项目摘要

Our results were as follows :(1) Standardized lung cancer mortality was significantly correlated with NO_2 content in the air and temperature in Western Japan (e.g., a simultaneous increase of 1 ppb NO_2 and 1℃ of temperature corresponding to 1.9 male death and 0.42 female death per 100,000 population).(2) Temperature in the filter was affected by room temperature at the beginning of smoking, and a difference in temperature in the filter reduced with time.(3) An exposure of graded concentrations of BPDE to cultured cells induced a DNA repair at 37℃ And cell death through apoptosis at 40℃.(4) Fukuoka, Kumamoto, Okayama, and Sapporo were chosen because of a difference in temperature and lung cancer death rate. The BPDE-DNA adduct levels in peripheral lymphocytes from 439 normal male volunteers were measured using 5D11 antibody specific to BPDE-DNA adduct by flow cytometry. As peripheral lymphocytes included BPDE-DNA adduct-positive cells and negative-cells, we calculated proportions of adduct-positive cells, mean adduct levels, and their products as a total adduct level. The proportion of positive cells was significantly higher in Sapporo, high lung cancer death rate and low temperature, than other cities (p<0.001), and Fukuoka, high death rate and high temperature, contained both higher and lower adduct-positive cell groups. Total BPDE-DNA adduct levels were also higher in Sapporo than the other cities (p<0.001). However, we failed to find significant differences in BPDE-DNA adduct between the younger and elder or between smokers and nonsmokers and regional differences in mean adduct level.

我们的结果如下：（1）标准化肺癌死亡率与日本西部空气中的NO_2含量和温度显著相关（例如，NO_2浓度每升高1 ppb，气温每升高1℃，每10万人中男性死亡1.9人，女性死亡0.42人。(2)在吸烟开始时，过滤嘴中的温度受室温影响，并且过滤嘴中的温差随时间减小。(3)不同浓度的BPDE在37℃时可诱导细胞DNA修复，40℃时可诱导细胞凋亡。(4)选择福冈、熊本、冈山和札幌是因为温度和肺癌死亡率的差异。应用抗BPDE-DNA加合物抗体5D_（11），用流式细胞仪检测了439名正常男性志愿者外周血淋巴细胞中BPDE-DNA加合物的含量。由于外周血淋巴细胞包括BPDE-DNA加合物阳性细胞和阴性细胞，我们计算了加合物阳性细胞的比例，平均加合物水平，以及它们的产物作为总加合物水平。肺癌死亡率高、气温低的札幌阳性细胞比例显著高于其他城市（p<0.001），死亡率高、气温高的福冈同时含有较高和较低的内收阳性细胞群。札幌的总BPDE-DNA加合物水平也高于其他城市（p<0.001）。然而，我们没有发现年轻人和老年人之间或吸烟者和非吸烟者之间的BPDE-DNA加合物的显着差异，以及平均加合物水平的地区差异。