| Main chronic toxicity of benzene is nervous system damage and hematopoietic damage. Benzene is an established human carcinogen. Damage of genetic materials caused by metabolites of benzene is one of the important mechanisms of carcinogenicity of benzene. In this paper, we selected benzene workers in an automobile manufacturing enterprise. The cytokinesis-block micronucleus (CBMN) assay was used to detect chromosomal damage. We also discussed the relationship between the white blood cell count and chromosomal damage. With method of polymerase chain reaction-restriction fragments length polymorphism (PCR-RFLP), genetic polymorphisms in some genes of cell cycle control were detected to discuss the gene-environmental factors of susceptibility to genetic damage, thus provides a reference for looking for sensitive and early effect biomarkers of benzene induced health problems and helps to identify susceptible populations and further strengthen the work of occupational health surveillance.Gas chromatographic was used to detect the concentration of benzene in the air of workplace. Benzene concentrations were all under0.6mg/m3at each point, which was lower than the present permissible exposure limit of benzene in china (PC-TWA=6mg/m3). According to the work process, we divided workers of different workshops and types into low exposure group, medium-exposure group and high exposure group based on benzene exposure opportunity. A total of825workers including737benzene-exposed workers and88unexposed controls were recruited.The results showed that, rate of nervous system damage in the benzene group was higher than the controls. Differences of symptoms of hematopoietic system damage were not found between benzene-exposed group and control group. The blood test was conducted twice among benzene exposed-workers whose WBC count were lower than4.5×109/L in the first test within three months. We found low concentrations of benzene exposure could still cause white blood cell count decrease, red blood cell count decrease and hemoglobin decrease. It shows that long-term exposure to benzene of low concentration still produce blood toxicity. The exposed subjects were classified according to WBC count as normal, unstable or low WBC group.We used Cytokinesis-block micronucleus (CBMN) assay in peripheral blood lymphocytes for chromosomal damage detection of461benzene exposed-workers and88controls. The results showed that:(1) The average MN frequency of long distance exposed group, middle distance exposed group and short distance exposed group were (2.15±2.06)%o,(2.19±1.83)‰and (2.02±1.75)‰, which were higher than that of control group, whose MN frequency was (1.19±1.68)‰, at81%,84%and69%, respectively. The difference was statistically significant (p<0.001).(2) Using the95%upper limit of the MN frequency in the control group as the limit value, normal rate of the micronucleus should be≤4‰in our study population. Workers with MN frequency higher than4‰were considered as chromosomal damage.(3) White blood cell count decrease is the earliest and most common manifestation of benzene induced hematologic toxicity. This study found that with the decrease of white blood cell count the chromosomal damage rate was increased. The chromosomal damage rate of controls was2.3%. The average MN frequency of benzene-exposed workers of normal WBC group, unstable WBC group and low WBC group were (1.84±1.98)‰,(2.18±1.73)‰and (2.32±1.95)‰, which were higher than the control group; There chromosomal damage rate were7.5%,11.2%and13.1%, which has a liner trend with the control group (χ2=8.271, P=0.004).(4)The average MN frequency of benzene-exposed workers of normal WBC group was53%higher than controls with normal WBC. It prompted that MN frequency rises before WBC decreases among benzene-exposed workers.Although under the same exposure conditions, different individuals may have different degree of genetic damage. It prompts the different susceptibility of genetic damage in different benzene-exposed individuals. Polymorphisms of p21Ex2+98 C>A, MDM2Dell518、MDM2IVS1+309T>G、p14(ARF) g.9792T>G, p14(ARF)g.22008G>A and p14(ARF) g.26294G>A were detected. We analyzed the relationships of genotypes, haplotypes and haplotype pairs with MN frequency:(1) After balancing of other factors, age and benzene exposure may be the risk factors of the increase of average MN frequency. Those who carry variant allele of p21Ex2+98C>A and p14(ARF) g.22008G>A had lower MN frequency than those who carried wild genotype.(2) There was interaction of benzene and MDM2Del1518on chromosome damage. Those who carry variant allele of MDM2Del1518had lower MN frequency than those who carried wild genotype only in the low exposure group.(3) Average MN frequency of workers carrying p14(ARF) gene TGA haplotype was higher than those with wild-type TGG haplotype (FR=1.16, FR95%CI=1.01-1.33).In conclusion, long-term exposure to low concentration benzene still produces chromosomal damage. It may occur before WBC decrease among benzene-exposed workers.The roles of environmental factors and genetic factors are both important in benzene induced chromosome damage. Age and increasing opportunity of benzene exposure are the risk factors of benzene induced genetic damage. p21, MDM2and p14(ARF) have a certain relationship with susceptibility of benzene induced genetic damage. It suggested that health education and occupational health care should be strengthened. Susceptible populations screening, early detection of health damage are suggested to protect workers’ health. |
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