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

本研究的目的是探讨石棉接触工人血清P53蛋白水平的分布与累积暴露、肺功能、吸烟及其他混杂因素的关系。研究对象是从500多名生产石棉和其他类型矿物纤维的工人中挑选的120名男性员工。在得到每个参与者的知情同意后，我们在1997年、1998年和1999年利用商业可获得的酶联免疫吸附试验试剂盒检测了血清泛素性和突变型p53蛋白(分别为PAN-P53和突变型P53)水平。此外，还测定了尿中8-羟基-2‘-脱氧鸟苷水平，作为氧合损伤的指标。到本研究时，他们的肺功能水平和胸部X线片已经每年测量超过12年。我们计算了每个受试者肺活量指数的年变化作为线性REG…的斜率血清PAN-P53平均浓度在50-75pg/ml左右，分布略偏于阳性。在1997年、1998年和1999年测量的泛P53水平之间观察到显著的正相关。在突变型P53浓度的情况下也有类似的趋势。其中一个有趣的结果是，PAN-P53水平高的受试者倾向于一秒用力呼气量(FEV1)下降的斜率更大。当根据PAN-P53浓度水平将他们划分为季度时，那些PAN-P53水平最高的季度显示出比其他受试者更快的年下降(FEV1平均下降-48毫升/年)(第二高、第三高和最低季度受试者的FEV1平均下降分别为-34、-33和-40毫升/年)。即使在调整了吸烟、职业暴露和个体的FEV1水平后，它们之间的差异仍有统计学意义(p=0.027)。因此，肺功能下降的加速和P53抑癌基因的激活可能是共同的倾向。血清P53水平与累积接触石棉的关系目前正在详细研究中。较少

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