Benchmark Doses Based on Abnormality of WBC or Micronucleus Frequency in Benzene-Exposed Chinese Workers.

OBJECTIVES: The aim of the study was to calculate benchmark dose for chromosomal damage and reduced white blood cell (WBC) associated with exposure to benzene (BZ). METHODS: A group of 317 exposed workers and 102 controls were examined for WBC count and genotoxicity by micronucleus (MN) frequency. The cumulative exposure concentration of BZ was calculated by ambient air BZ concentration at worksites in conjunction with job type and associated service duration. RESULTS: MN frequency (P < 0.01) was higher and WBC count was lower (P < 0.01) in exposed workers on average than in the controls. MN frequency was a more sensitive than WBC; workers older than 30 were more susceptible to abnormal MN frequency and WBC count reduction than those younger than 30. CONCLUSIONS: Benchmark dose estimates indicated that BZ exposure at levels below the current occupational exposure standard can induce genotoxicity and hematotoxicity.

Are polymorphisms in metabolism protective or a risk for reduced white blood cell counts in a Chinese population with low occupational benzene exposures?

BACKGROUND: Genetic variations in metabolic enzyme genes may enhance hematotoxicity in benzene-exposed populations. OBJECTIVE: To investigate the association between polymorphisms of metabolism genes and white blood cells (WBCs). METHODS: Three hundred and eighty-five benzene-exposed workers and 220 unexposed indoor workers were recruited in China. We explored the relationship between metabolic enzymes polymorphisms [glutathione S-transferase T1/M1 (GSTT1/M1) null, glutathione S-transferase P1 (GSTP1)rs1695, Cytochrome P450 2E1 (CYP2E1) rs3813867, rs2031920, rs6413432, microsomal epoxide hydrolase (mEH) rs1051740, rs2234922] by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) analysis and WBC. RESULTS: The exposed group had lower WBC counts (P<0·001) than the unexposed group. Increased susceptibility to hematotoxicity, as evidenced by lower WBC counts, was found in workers with null-GSTT1 (P = 0·045), null-GSTM1 (P = 0·030), rs2031920 (P = 0·020), and rs3813867 (P = 0·014) genotypes. White blood cell counts were also lower in workers with null-GSTT1 and null-GSTM after adjusting for age, gender, smoking, and alcohol consumption. CONCLUSION: Null-GSTT1 and null-GSTM1 genotypes and Cytochrome P4502E1 (CYP2E1: rs2031920, rs3813867) may support the hematotoxicity of benzene-exposed workers in China, and we can make use of it to select susceptible population.

Effect of polymorphic metabolizing genes on micronucleus frequencies among benzene-exposed shoe workers in China.

It is well-known that metabolism of benzene is required for the induction of toxicity and consequent health problems. Therefore, genetic variation in benzene (BZ) metabolism genes can influence health outcomes. However, large population studies are needed to provide more evidence for such relationship. We have conducted a large population investigation (385 BZ-exposed shoe workers and 197 matched healthy controls) on the association between inheritance of certain BZ metabolizing genes and the expression of micronuclei (MN). The latter was based on the cytokinesis-blocked MN assay. We analyzed the polymorphisms of GSTM1, GSTT1, GSTP1 (rs1695), CYP2E1 (rs3813867), CYP2E1 (rs2031920), CYP2E1 (rs6413432), mEH exon 3 (rs1051740), mEH exon 4 (rs2234922). Univariate Poisson regression analysis demonstrated that the BZ-exposed workers had significantly increased MN frequency compared with the controls (FR=1.84, 95% CI: 1.56-2.18; P<0.001), and showed a cumulative exposure dose-response relationship. The CYP2E1 rs3813867 mutant allele (CC+GC) (FR 1.15, 95% CI 1.02-1.29; P=0.020) and rs2031920 variant allele (CT+TT) (FR=1.23, 95% CI: 1.09-1.37, P<0.01) was associated with higher MN frequency significantly compared with the wild genotype separately. Furthermore, the MN frequency in rs2031920 variant allele (CT+TT) (FR=1.17, 95% CI: 1.04-1.31, P<0.01) was also higher than the wild genotype when the age, gender and cumulative exposure dose was adjusted in Poisson regression. In addition, the CYP2E1, however, GSTM1null, GSTT1null, GSTP1 rs1695, rs6413432, rs1051740 and rs2234922 polymorphisms showed no association with MN frequency. Our results indicate that two promoter polymorphisms in the CYP2E1 gene, especially the rs2031920 variant allele, were involved with the BZ-induction of MN and may contribute to risk of cancer among exposed workers.

[Clinical analysis and laboratory findings in a patient with acquired hemophilia A].

In order to analyze the clinical features and laboratory findings in patients with acquired hemophilia A, one case of acquired hemophilia A was studied, the medical history, clinical features, ultrasonography and laboratory examination including activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT) and FVIII:C, FIX:C, FXI:C, FXII:C ratio, as well as medical treatment were analyzed. The results showed 99.3 sec of APTT, 13 sec of PT, and 13.5 sec of TT, 2% of FVIII:C, 7% of FIX:C, 9% of FXI:C and 21% of FXII:C. The prolongation of APTT could not be completely corrected by mixing the patient plasma with an equal volume of normal fresh plasma; the APTT increased with prolongation of incubation time, when patient plasma was mixed with an equal volume of normal fresh plasma and incubated at 37 degrees C. The plasma FVIII:C, FIX:C, FXI:C and FXII:C levels in patient were 6%, 75%, 95% and 123% respectively, when patient's plasma was diluted by tenfold and mixed with an equal volume of non-diluted normal plasma. FVIII inhibitor in the patient's serum was at a level >32.0 Bethesda units/ml after acquired hemophilia was diagnosed, the patient was admitted to hospital and given orally prednisone and azathioprine therapy. One month later, clinical status of the patient were improved with 33.3 seconds of APTT, 128% of FVIII level and elimination of FVIII inhibitor. In conclusion, inquiring case history, analyzing imaging results, detecting level of APTT, performing dilution test and assaying titer of FVIII inhibitor can reduce misdiagnosis and wrong therapy for patients with acquired hemophilia A. The FVIII inhibitor can be eliminated and function of clotting can be recovered by using immunosuppressive therapy.

[Dynamic change of plasma prethrombotic state molecular marker levels in perioperative period of patients and its clinical significance].

This study was aimed to investigate the dynamic changes of plasma prethrombotic state molecular marker levels during perioperation of patients and to provide laboratorial evidence for clinical diagnosis of these patients so as to take intervenient measure to high risk patients. 40 patients with gynecological and urological malignant tumors (without metastasis) and 20 patients with benign tumors and 20 healthy individuals were selected for analysis. The levels of plasm prethrombotic state molecular markers including TF, TFPI, TpP, PAI-1, P-S, TAT and D-D were measured by using ELISA method and transmission immunity nephelometry. The results showed that the levels of TF, TpP, D-D, P-S and TAT in plasma of patients with malignant tumors at 6 hours after operation were higher than that before operation, but the levels of TFPI and PAI-1 in these patients after operation were lower than before operation, and there was significant difference as compared with the levels of these markers before operation. At day 3 after operation, the levels of TF, TpP and D-D continuously increased; the level of PAI-1 begins to elevate, there were significant difference in comparison with that before operation; the levels of P-S and TAT decreased, but still were higher than that before operation. At day 7 after operation, the levels of TpP, TAT, P-S, TFPI and PAI-1 returned to levels before operation, but the levels of TF and D-D were still higher than that before operation, and showed significant difference from that before operation. In patients with benign tumors and non-operation patients, the levels of prethrombotic state molecular markers mentioned above at different points of time after operation did not present difference, except levels of TF and D-D that at 6 hours after operation were higher than that before operation. It is concluded that at 6 hours after operation of patients with gynecological and urological malignant tumours, the plasma levels of prethrombotic state molecular markers are in higher state of coagulation and fibrinolysis, at 3 days after operation these levels are mainly in coagulation state. At 7 days after operation, the level of these markers returned to levels before operation. At 6 hours after operation the levels of these markers in patients with benign tumors are in mild coagulation state.