Serum plasminogen as a potential biomarker for the effects of low-dose benzene exposure.

Exposure to low-dose benzene may lead to hematotoxicity and cause health problems. Though peripheral blood cell count is widely used in benzene exposure assessment and health risk assessment, the reports regarding the effects of low-dose benzene exposure on blood cell count remain inconsistent. To uncover more sensitive biomarkers for low-dose benzene exposure, our previous study screened out three potential serum proteins-plasminogen (PLG), platelet basic protein (PBP) and apolipoprotein B100 (ApoB100)-as biomarkers from chronic benzene poisoning patients by using proteomic analysis. In the present study, we verify the three serum proteins as biomarkers for the effects of low-dose benzene exposure in a large low-dose benzene exposure population. The study showed that serum PLG increased in benzene exposed workers and was positively correlated with benzene exposure levels. However, no significant changes in serum PBP or ApoB100 were found in the benzene exposed workers. To explore whether the candidate serum proteins are associated with hematotoxicity, the study population was regrouped into two groups, based on their WBC counts. Our results showed that the workers with high serum PLG levels suffered higher risk of WBC abnormalities than did workers with low serum PLG levels. Taken together, these findings indicate that the increase in serum PLG might be associated with low-dose benzene exposure and benzene-induced hematotoxicity. Thus, we suggest serum PLG could be used as a potential biomarker for the effects of low-dose benzene exposure.

Characterization of liver injury associated with hypersensitive skin reactions induced by trichloroethylene in the guinea pig maximization test.

Trichloroethylene (TCE) can induce non-dose-related hepatitis, possibly classified as delayed-type hypersensitivity (immune-mediated hepatitis), as well as dose-related toxic liver injury. However, the difference in pathophysiology between the two kinds of hepatitis remains unknown. This study aimed to characterize the liver injury associated with hypersensitive skin reactions induced by TCE in guinea pigs. As a model of dose-related acute toxic liver injury, the animals were treated with intradermal injection (ii) (0, 167, 500, 1500 or 4500 mg/kg of TCE) or dermal patch (dp) (0 or 900 mg/kg of TCE). The guinea pig maximization test (GPMT) was also carried out as a model of immune-mediated liver injury, in which the total TCE dosage was below 340 mg/kg. In the group of TCE 4500 mg/kg (ii), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) increased (p<0.01), while total protein and globulin decreased (p<0.05). Evident fatty degeneration, hepatic sinusoid dilation and inflammatory cell infiltration were observed. No significant change was found in animals treated with TCE of doses below 500 mg/kg (ii) or 900 mg/kg (dp). In the GPMT, sensitization rates of TCE-induced dermal allergy were 66%. ALT, AST, lactate dehydrogenase and the relative liver weight increased significantly (p<0.05) while albumin, IgA and gamma-glutamyl transpeptidase decreased significantly (p<0.05). Lesions of ballooning changes were observed in liver pathology. Thus, TCE could cause both acute-type toxic liver injury and immune-mediated liver injury, the so-called delayed-type hypersensitivity at doses below the dosage for toxic liver injury. Interestingly, the histopathological features were quite different: fatty degeneration was most prominent in the former, and ballooning in the latter.