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

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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