Research On The Exposure And Early Effect Biomarkers In Mice And Workers Exposed To Benzene

Objectives The study was designed to explore the health damage of benzene exposure, and the early biological indicators reflecting benzene exposure and health effects in body. The S-phenylmercapturic acid(SPMA) and 8-hydroxy-2’-deoxyguanosine(8-OHd G) in uric and hemogram of mice and benzen-exposure workers were measured.The correlation between 8-OHd G and hemogram,SPMA was analysed in order to explore whether the 8-OHd G is an effect index reflecting the DNA oxidative damage induced by benzene exposure.Methods Animal experimentation: A total of 120 Kunming male mice were exposed to 0 mg/m3,375mg/m3,750mg/m3,1500mg/m3 of benzene for 2h each day,5 days each week,in static inhalation cabin for 3 months. In each group,ten mice were randomly sacrificed every a month.The pathomorphology of lung,liver and kidney of mice was observed.The hemogram, polychromatic erythrocytes(PCE) and SPMA and 8-OHd G concentration in urine were measured.The changes of indexes above-mentioned among the different doses and exposure time were observed.The correlation between 8-OHd G and hemogram,SPMA was analysed in order to screen the indexes with early change induced by benzene exposure. Epidemiological study: A total of 86 benzen-exposed workers was chose and their general population information was collected by occuptional epidemiological survey. The hemogram,SPMA and 8-OHd G concentration in urine of the workers were measured.The correlation between 8-OHd G and hemogram,SPMA was analysed.Results 1 Animal experimentation: In the low dose group, the alveolar septum of the lung tissue of mice was slightly thickened, the middle dose group and high dose group were more serious, and the alveolar septum thickening was obvious, and there was a significant dilation and congestion. The low dose group of visible liver cells were slightly edema, the middle dose group of mice liver cells visible protein exudation edema, liver cable slightly disordered, mice in high dose group showed more regeneration of liver cells, nuclei pyknosis, hepatic cord disorders obvious edema, severe. In low dose group, kindey tissue showed slight edema and red dye, and the kindey tissue in middle and high dose group showed edema, increased cell volume and dilated congestion. With increaseof the dose, the number of WBC, RBC and lymphocyte reduced(P<0.05). With the increase of the dose and the extension of exposure time, the rate of bone marrow cell micronucleus increased(P<0.05). Compared with the low and medium dose group, the Sphenylmercapturic acid in urine in high dose group increased(P<0.05). Compared with the 1st,2nd month, the content of S-phenylmercapturic acid in urine in the 3rd month markedly increased(P<0.05). With the increase of the dose and the extension of exposure time, the content of 8-hydroxy-2-deoxyguanosine in urine increased(P<0.05). In the three mouth, The correlation coefficient between S-phenylmercapturic acid and 8-hydroxy-2-deoxyguanosine was 0.626,0.769 and 0.705(P<0.01). 2 Epidemiological study: Compared with the control group, the WBC decreased in the workers with 1-5 years and 6-10 years exposure history of benzene and the RBC increased(P<0.05). Compared with the control group, the concentration of SPMA and 8-OHd G in urine increased in the workers with 1-5 years and 6-10 years exposure history of benzene(P<0.05). The 8-OHd G content in urine of the benzene-exposed workers who smoked frequently was higher than the workers who did not smoke or smoked occasionally. The 8-OHd G content in urine of the benzene-exposed workers who drinked frequently was higher than the workers who did not drink or drinked occasionally. The concentrations of SPMA and 8-OHd G in urine in the workers without personal protective measures were higher than the workers with personal protective measures. There was positive correlation between the concentrations of SPMA and 8-OHd G in urine,and the correlation coefficient was 0.786(P<0.001).Conclusions 1 Subchronic exposure to benzene may induce the pathomorphology changes in lung,liver and kidney and damage of blood system in mice. 2 The 8-OHd G in urine may reflect the DNA oxidative damage induced by benzene exposure. There was a good correlation with 8-OHd G and SPMA.3 The hemogram,SPMA and 8-OHd G in urine are very sensitive to benzene exposure and reflect early health damage.