WU Yiming, WANG Xinchao, CHEN Chen, MA Yuying, XU Yubao,LI Hong,
(Department of Occupational Health and Health Toxicology, Henan Medical University, Zhengzhou 450052, P.R.China)
SHI Xianglin
(Pathology and Physiology Research, NIOSH, Morgantown, WV 26505, USA)

Polycyclic Aromatic Hydrocarbons(PAHs),first determined as a sort of chemical carcinogen, can exist in chemical substance such as coal tar pitch (CTP) and coke oven volatiles (COV). The carcinogenesis of PAHs has been confirmed by epidemiological studies among high risk population and animal experiments. The excessive mortality of lung cancer has been found in workers exposed to CTP and COV. Lung cancer can be induced in rats or mice with CTP by inspiring CTP fog or intratracheal instillations. The latest advance in the study of molecular biology has been applied to the fields of occupational cancer prevention and diagnosis. The study of the amount, effect, and injury of carcinogen with biomarkers has become one of the imporant methods for the early detection for occupational lung cancer.
In June of 1994, 22 workers exposed to CTP and COV were examined for P21 with the method of Western blotting in our laboratory, the mean P21 value was (3 484.4±1 915.8), 2 of them were determined as P21 positive individuals. In the second test(1997), serum P21 level(3 773.3±1 033.7) were measured again among the same workers exposed to CTP and COV in order to evaluate their clinical value by follow-up longitudinal observation. As P21 detective method is complicated, and the regents used are expensive and certain facilities are needed, which limit P21 follow-up observation each year, it is very useful for screening individuals at risk of cancer with related criteria to estimate P21 values. Certain markers related to P21 can be selected as to predict the lung cancer. 24 workers exposed to CTP and 25 exposed to COV were studied by determining serum SOD activity, LPO concentration, and peripheral blood lymphocyte SCE frequency in this cohort. P21 level was longitudinal compared to that detected 2 years ago. The data described above was analysed. The correlation among them was studied by multi-factors analysis.
The results showed that serum SOD activity was significantly lower (P<0.01) in the exposed group (EG) than that in the normal group (NG). However ,the serum LPO concentration was much higher (P<0.01) in the EG than that in the NG. SCE rate in the EG was significantly higher (P<0.01) than that in the NG. The serum P21 levels were apparently increased in workers exposed to CTP and COV compared to those in the NG(P<0.01,respectively). Three workers exposed to COV and to CTP were given a definite recognized as P21 positive persons, because their P21 level were five fold higher than the average P21 value of the normal control group.
The average P21 value in followed-up workers in the second study increased by 288.9 over the P21 level measured 2 years ago and no lung cancer was found during follow-up study. Although the P21 level of the two workers who were believed as lung cancer risk persons because of their higher P21 levels 2 years ago went down in this cohort study, their P21 levels were still 3.95 and 4.59 fold higher than the mean P21 value of the NG.
The correlation coefficient (r) between SCE and P21 was 0.425 by correlation calculation. The result showed that there was a liner correlation between SCE and P21, indicating that the individuals whose SCE rate was beyond higher may simultaneously have a higher P21 level.
Among exposed workers, the SCE rate and the P21 value of the smokers were slightly higher than those of the non-smokers , but there were no significantly statistical differences between them(P>0.05). Perhaps it is because the harm resulting from the air pollution of the working environment to the genetic effect was much stronger than that of smoking, the genetic effect of smoking may be concealed.
The follow-up study indicated that P21 increased with longer exposure to CTP and COV. The two workers whose P21 values determined as positive 2 years ago had not developed to lung cancer. It may be due to the repair of DNA or the long incubation period of occupational cancer. These results suggest that CTP and COV can cause biological membrane injury of the exposure workers and can change the genetic effects. The detailed relationship between ras P21 and lung cancer can be observed by undertaking animal experiments with CTP or COV.

基金项目：河南省自然科学基金资助项目 97330001 984020300

2000-01-05 收稿 (WU Yiming WANG Xinchao CHEN Chen MA Yuying XU Yubao LI Hong SHI Xianglin)