A Molecular Epidemiologic Study on The Relations Between Serum p53 Protein Concentration and Cumulative Exposure to Asbestos

血清p53蛋白浓度与石棉累积暴露关系的分子流行病学研究

• 批准号: 10670367
• 负责人: NAKADATE Toshio
• 金额: $ 1.86万
• 依托单位: Showa University (1999)Tokyo Women's Medical University (1998)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670367/
• 关键词: Obstructive Lung Disease; Forced Expiratory Voleme in One Second; Serum p53 Protein; Urine 8-Hydroxy-2' deoxyguanosine; Longitudinal Study; Prediction; Asbestos; Meneral Fibers; 閉寒性肺疾患; 血清ρ53蛋白; 尿中80hdG

The objective of this study was to evaluate the distribution of serum level of p53 protein, products of p53 tumor suppressor gene, among asbestos-exposed workers, in relation to cumulative exposure as well as pulmonary function, smoking, and other confounding factors.Study subjects were a total 120 male employees selected from a cohort which was consisted of over 500 workers manufacturing asbestos and some other types of mineral fibers. After given a informed consent from each participant, we examined serum pantropic and mutant p53 protein (pan-p53 and mutant-p53, respectively) levels in 1997, in 1998, and in 1999, utilizing commercially available ELISA kits. In addition, 8-hydroxy-2'-deoxyguanosine level in urine was also measured, as an index of oxygenating damage. Their pulmonary function level and chest X-ray radiogram had been measured annually for over 12 years by the time of this study. We calculated annual change in spirometric indices of each subject as a slope of a linear reg … More ression of the index on age.The mean level of serum pan-p53 concentration was around 50-75 pg/ml, and distributed with slight skewness towards positive. Significantly positive association was observed among the pan-p53 levels measured in 1997, in 1998, and in 1999. Similar tendency was noted in the case of mutant p53 concentration. One of the interesting results was that subjects with high pan-p53 level tended to have steeper slope of decline in forced expiratory volume in one second (FEV1). When they were divided into quarters based on the level of pan-p53 concentration, those in the highest quarter in terms of the pan-p53 level showed a faster annual decline (-48 ml/year as a mean FEV1 decline) than other subjects (-34, -33, and -40 ml/year as a mean FEV1 decline for the second highest, the third highest, and the lowest quarter subjects, respectively). The difference among them was statistically significant (p=0.027) even after adjustment for cigarette smoking, occupational exposure, and the level of FEV1 of individual subject. Thus, there might be a shared liability to both acceleration of pulmonary function decline and activation of p53 tumor suppressor gene. The association of serum p53 level with cumulative exposure to asbestos is now under consideration in detail. Less

本研究旨在探讨石棉接触工人血清p53蛋白（p53抑癌基因产物）水平的分布及其与石棉累积接触量、肺功能、吸烟、研究对象是从500多名石棉和其他类型的工人中选出的120名男性雇员。矿物纤维在获得每位参与者的知情同意后，我们分别于1997年、1998年和1999年使用市售的ELISA试剂盒检测了血清泛嗜性和突变型p53蛋白（分别为泛p53和突变型p53）水平。此外，还测量了尿中8-羟基-2 '-脱氧鸟苷水平，作为氧合损伤的指标。到本研究时，他们每年都测量肺功能水平和胸部X线片，已超过12年。我们计算了每个受试者肺量指数的年变化，作为线性回归方程的斜率。 ...更多信息 血清pan-p53浓度平均值为50-75 pg/ml，呈轻度偏阳性分布。在1997年、1998年和1999年测量的泛p53水平之间观察到显著正相关。在突变型p53浓度的情况下注意到类似的趋势。一个有趣的结果是，具有高泛p53水平的受试者倾向于具有一秒用力呼气量（FEV 1）下降的陡峭斜率。当根据pan-p53浓度水平将受试者分为四个季度时，pan-p53水平最高四个季度的受试者显示出比其他受试者（第二高、第三高和最低四个季度受试者的平均FEV 1下降分别为-34、-33和-40 ml/年）更快的年下降（平均FEV 1下降为-48 ml/年）。即使在调整吸烟、职业暴露和个体受试者的FEV 1水平后，他们之间的差异也具有统计学意义（p=0.027）。因此，肺功能的加速下降和p53抑癌基因的激活可能是共同的责任。血清p53水平与石棉累积暴露的关系正在详细研究中。少

项目成果

山野優子: "第3章 環境発掘と酸化的DNA損傷-曝露評価-環境発がんのブラックボックスを探る-産業分子疫学のチャレンジ-"労働科学研究所出版部. 195 (1999)

山野裕子：《第三章环境挖掘与氧化DNA损伤-暴露评估-探索环境致癌的黑匣子-工业分子流行病学的挑战-》劳动科学研究所出版部195（1999）。

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山野優子: "酸化ストレス指標80HdG値と青年期における生活習慣との関係"産業衛生学雑誌. 41・増刊. 221 (1999)

Yuko Yamano：“氧化应激指数80HdG水平与青春期生活习惯的关系”工业卫生杂志41，特别版（1999）。

Nakadate T.: "Pre-existing pulmonary fibrosis and subsequent acceleration of FEV1 decline."Excerpta Medica International Congress Series. ICS1153. 351-354 (1998)

Nakadate T.：“预先存在的肺纤维化和随后 FEV1 下降的加速。”医学摘录国际大会系列。

Hara K, Hanada T, Yamano Y, Pan G, Ichiba M, Wang Y, Zhang J et al: "Urinary I-Hydroxypyrene as a biomarker for exposure to polycyclic aromatic hydrocarbons in Chinese coak oven workers"Nagoya Medical Journal. 42. 157-169 (1998)

Hara K、Hanada T、Yamano Y、Pan G、Ichiba M、Wang Y、Zhang J 等人：“尿 I-羟基芘作为中国烤炉工人接触多环芳烃的生物标志物”名古屋医学杂志。