Mechanism of Learning and Memory Impairment in Rats Exposed to Arsenic and/or Fluoride Based on Microbiome and Metabolome.

Objective: Arsenic (As) and fluoride (F) are two of the most common elements contaminating groundwater resources. A growing number of studies have found that As and F can cause neurotoxicity in infants and children, leading to cognitive, learning, and memory impairments. However, early biomarkers of learning and memory impairment induced by As and/or F remain unclear. In the present study, the mechanisms by which As and/or F cause learning memory impairment are explored at the multi-omics level (microbiome and metabolome). Methods: We stablished an SD rats model exposed to arsenic and/or fluoride from intrauterine to adult period. Results: Arsenic and/fluoride exposed groups showed reduced neurobehavioral performance and lesions in the hippocampal CA1 region. 16S rRNA gene sequencing revealed that As and/or F exposure significantly altered the composition and diversity of the gut microbiome，featuring the Lachnospiraceae_NK4A136_group, Ruminococcus_1, Prevotellaceae_NK3B31_group, [Eubacterium]_xylanophilum_group. Metabolome analysis showed that As and/or F-induced learning and memory impairment may be related to tryptophan, lipoic acid, glutamate, gamma-aminobutyric acidergic (GABAergic) synapse, and arachidonic acid (AA) metabolism. The gut microbiota, metabolites, and learning memory indicators were significantly correlated. Conclusion: Learning memory impairment triggered by As and/or F exposure may be mediated by different gut microbes and their associated metabolites.

Nano-Calcium Carbonate Affect the Respiratory and Function Through Inducing Oxidative Stress: A Cross-sectional Study Among Occupational Exposure of Workers and a Further Research for Underlying Mechanisms.

OBJECTIVE: The aim of the study is to investigate whether nano-calcium carbonate (nano-CaCO 3 ) occupational exposure could induce adverse health effects in workers. METHODS: A cross-sectional study was conducted in a nano-CaCO 3 manufacturing plant in China. Then, we have studied the dynamic distribution of nano-CaCO 3 in nude mice and examined the oxidative damage biomarkers of subchronic administrated nano-CaCO 3 on Sprague-Dawley rats. RESULTS: The forced vital capacity (%) and the ratio of FEV1 to FVC is the rate of one second of workers were significantly decreased than unexposed individuals. Dynamic imaging in mice of fluorescence labeled nano-CaCO 3 showed relatively high uptake and slow washout in lung. Similar to population data, the decline in serum glutathione level and elevation in serum MDA were observed in nano-CaCO 3 -infected Sprague-Dawley rats. CONCLUSIONS: We found that nano-CaCO 3 exposure may result in the poor pulmonary function in workers and lead to the changes of oxidative stress indexes.

Mechanism of subchronic vinyl chloride exposure combined with a high-fat diet on hepatic steatosis.

Vinyl chloride (VC) is a common industrial organic chlorine and environmental pollutant. In recent years, the dietary structure of residents especially Chinese has gradually shifted to western dietary patterns. VC aggravates dietary fatty acid-induced hepatic steatosis, but its mechanism is still unclear. And if the risk factors for steatosis persist, more severe diseases such as fibrosis and cirrhosis will occur. Therefore, we studied the effects and mechanisms of VC (160 and 800 mg/m3 ) and its metabolite (chloroacetaldehyde, 2.25, 4.5, and 9 µM) on hepatic steatosis of high-fat diet (HFD)-fed mice and palmitic acid (PA, 100 µM) treated HepG2 cells. Liver and serum biochemical indicators and pathological staining of the liver showed that the hepatic steatosis of VC combined with HFD groups was more severe than that of single-exposure groups (HFD group, low-dose VC group, and high-dose VC group). Moreover, VC enhanced HFD-induced oxidative stress (OS) and endoplasmic reticulum stress (ERS) and further upregulated the expression of sterol regulatory element-binding protein 1 (SREBP-1) and FAS. Besides, antioxidants and ERS inhibitors reduced the steatosis of HepG2 cells induced by VC metabolites and PA. These results suggest that VC exposure can enhance the degree of hepatic steatosis in HFD-fed mice. VC combined with HFD led to OS and ERS and upregulated the expression of de novo lipogenesis-related proteins, which may be related to the occurrence of hepatic steatosis. And the increased expression of CYP2E1 induced by VC combined with HFD may be the cause of OS.

Relative Telomere Length in Peripheral Blood Cells and Hypertension Risk among Mine Workers: A Case-Control Study in Chinese Coal Miners.

Hypertension is a common chronic disease in middle-aged and elderly people and is an important risk factor for many cardiovascular diseases. Its pathogenesis remains unclear. Epidemiological studies have found that the loss of telomere length in peripheral blood cells can increase the risk of coronary heart disease, myocardial infarction, and other diseases. However, a correlation between loss of telomere length and hypertension has not been established. In this study, we aimed to explore the association between telomere length and the risk of essential hypertension (EH) in Chinese coal miners. A case-control study was performed with 215 EH patients and 222 healthy controls in a large coal mining group located in North China. Face-to-face interviews were conducted by trained staff with the necessary medical knowledge. Relative telomere length (RTL) was measured by a quantitative real-time PCR assay using DNA extracted from peripheral blood. In the control group, the age-adjusted RTL was statistically significantly lower in miners performing hard physical labour compared with nonphysical labour (P = 0.043). A significantly shorter age-adjusted RTL was found in the control group of participants who consumed alcohol regularly compared with those who do not consume alcohol (P = 0.024). Age-adjusted RTL was negatively correlated with body mass index (BMI) and alcohol consumption. Hypertension was also found to be significantly correlated with factors such as age, BMI, alcohol consumption, smoking, and tea consumption. Our results suggest that RTL is associated with hypertension in coal miners.

Role of endoplasmic reticulum stress and oxidative stress in vinyl chloride-induced hepatic steatosis in mice.

Vinyl chloride (VC) is a common industrial organochlorine, shown to cause hepatic angiosarcoma and hepatic steatosis. However, the role of endoplasmic reticulum stress (ERS) and oxidative stress (OS) in hepatic steatosis after subchronic exposure to VC in mice, is unclear. Based on body weight, forty healthy SPF male C57BL/6 J mice were randomly divided into a control group and three VC exposure groups (57.3, 286.7, and 1433.6 ppm) (n = 10 each). VC was administered by static inhalation in a 50 L sealed plexiglass inhalation chamber for 2 h per day, five days per week for 16 weeks. Serum and liver tissues were analyzed for liver enzymes and lipids. Hepatic cytochrome P450 2E1 (CYP2E1) and OS related indicators malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) were measured. The mRNA expressions of ERS downstream genes, including glycoregulatory protein-78 (GRP-78), sterol regulatory element binding protein-1 (SREBP-1), Acetyl-CoA carboxylase (ACC), and fatty acid synthase (FAS) were detected by real-time PCR (RT-PCR) and their protein levels examined by western blotting. The CYP2E1 levels increased after VC administration in a dose-dependent manner. MDA levels increased (P < .05) and SOD and GSH levels decreased (P < .05) in the liver of each group with the increase in the dose of VC. ERS and expressions of downstream genes (GRP-78, SREBP-1, ACC, and FAS) were enhanced after VC administration. These results suggested that OS and ERS could be induced by VC, which may lead to an increase in fatty acid synthesis in the liver, further aggravating hepatic steatosis.

Association between methylation of DNA damage response-related genes and DNA damage in hepatocytes of rats following subchronic exposure to vinyl chloride.

In the present study, we investigated the association between methylation of DNA damage response-related genes such as cyclin-dependent kinase inhibitor (CDKN)2A, Ras association (RalGDS/AF-6) domain family member (RASSF)1A, O6-methylguanine DNA methyltransferase (MGMT), Kirsten rat sarcoma viral oncogene homolog (KRAS), and spleen-associated tyrosine kinase (SYK) and DNA damage in hepatocytes of rats following subchronic exposure to vinyl chloride (VC). Sixty-four healthy rats were randomly divided into three VC exposure groups (5, 25, and 125 mg/kg) and an untreated negative control group (n = 16 each). VC was administered by intraperitoneal injection every other day for a total of three times a week. Eight randomly selected rats from each group were sacrificed at the end of 6 and 12 weeks, and liver tissue was harvested for the comet assay and for assessment of DNA methylation level and mRNA expression of related genes by PCR. Overall methylation levels in the genome of hepatocytes in VC-exposed rats were higher than those in the control group at 6 and 12 weeks (P < 0.05), although no differences were observed with regarding to dose (P > 0.05). After 12 weeks of exposure, differences in the methylation of RASSF1A and MGMT promoter regions were observed between the high-dose group and other groups (P < 0.05), whereas no differences were observed for the KRAS, SYK, and CDKN2A promoters (P > 0.05). These results suggest that DNA damage and increased genome-wide methylation are biomarkers for VC exposure and that RASSF1A and MGMT promoter methylation is related to the carcinogenic mechanism of VC.

Comparison of survival and tumor recurrence rates in patients undergoing liver transplantation for hepatitis B-related hepatocellular carcinoma using Milan, Shanghai Fudan and Hangzhou criteria.

OBJECTIVES: To assess the performance of the Milan, Shanghai Fudan and Hangzhou criteria based on a preoperative evaluation in patients undergoing liver transplantation (LT) for hepatitis B-related hepatocellular carcinoma (HCC). METHODS: Using a prospectively collected database, the data of consecutive patients with hepatitis B-related HCC undergoing LT at the Department of Liver Surgery of Ren Ji Hospital, School of Medicine, Shanghai Jiaotong University from January 2005 to December 2009 were reviewed. Overall survival and tumor recurrence rates of patients fulfilling the Milan, Shanghai Fudan and Hangzhou criteria were compared using log-rank test. RESULTS: Altogether 148 patients were enrolled in the study, among whom 88 fulfilled the Milan criteria and 24 and 39 were beyond Milan but within the Shanghai Fudan or Hangzhou criteria, respectively. After a median follow-up of 44 months, survival rates did not differ among the three groups (P = 0.8780). Recurrence rates were significantly higher for newly eligible patients by the Shanghai Fudan or Hangzhou criteria compared with those within the Milan criteria. CONCLUSIONS: The Milan criteria should be used as the preferred criteria for the selection of hepatitis B-related HCC for LT. Considering the high tumor recurrence rates and donor scarcity, a moderate expansion of the Milan criteria must be performed cautiously until high-quality clinical trials are conducted.

Correlation of chromosome damage and promoter methylation status of the DNA repair genes MGMT and hMLH1 in Chinese vinyl chloride monomer (VCM)-exposed workers.

OBJECTIVE: To explore the association of the methylation status of MGMT and hMLH1 with chromosome damage induced by vinyl chloride monomer (VCM). MATERIALS AND METHODS: Methylation of MGMT and hMLH1 was measured in 101 VCM-exposed workers by methylation-specific PCR. Chromosome damage in peripheral blood lymphocytes was measured by the cytokinesis-block micronucleus assay. The subjects were divided into chromosome damaged and non-damaged groups based on the normal reference value of micronuclei frequencies determined for two control groups. RESULTS: MGMT promoter methylation was detectable in 5 out of 49 chromosome damaged subjects, but not in the chromosome non-damaged subjects; there was a significant difference in MGMT methylation between the two groups (p < 0.05). CONCLUSIONS: We detected aberrant promoter methylation of MGMT in a small number of chromosome damaged VCM-exposed workers, but not in the chromosome non-damaged subjects. This preliminary observation warrants further investigation in a larger study.

Messenger RNA expression and genetic polymorphisms of cell cycle control genes and chromosomal aberrations in Chinese vinyl chloride monomer-exposed workers.

OBJECTIVE: To evaluate the expressions of p53, p21, and CCND1 in the peripheral blood lymphocytes of vinyl chloride monomer (VCM)-exposed workers and potential relationships with their exposures, polymorphisms, and chromosomal aberrations. METHODS: The study was performed on 77 occupationally VCM-exposed workers and 43 unexposed controls. The quantities of mRNA expression of p53, p21, and CCND1 genes were detected by real-time polymerase chain reaction. RESULTS: p53 mRNA expression of VCM-low- and high-exposure groups was significantly lower than that of nonexposed group (P < 0.001), but p21 mRNA expression of the two VCM-exposed groups was significantly higher than that of the nonexposed group (P < 0.001). This study did not find the relationship between chromosomal aberrations, genotypes, and the expression of p53, p21, and CCND1. CONCLUSIONS: Messenger RNA expressions of p53 and p21 are changed with VCM-exposure status.

Genotoxicity in vinyl chloride-exposed workers and its implication for occupational exposure limit.

BACKGROUND: Vinyl chloride monomer (VCM) is a colorless gas under room temperature and has been mostly used to produce polyvinyl chloride (PVC) since the 1970s. It is classified by the International Agency of Research on Cancer (IARC) as a known human carcinogen (Group 1). In this study, genetic damage in VCM workers was evaluated in relation to their occupational cumulative exposure to VCM. METHODS: Cytokinesis-block micronucleus assay was conducted in 229 VCM workers and 138 controls to detect chromosome damage in peripheral blood lymphocytes. The cumulative exposure dose (CED) of VCM was calculated based on the job type and duration of each worker and the workplace VCM concentration. Dose-response relationships between VCM CED and micronucleus frequency or chromosomal damage were evaluated, and benchmark doses (BMDs) estimated. RESULTS: Dose-response relationships between VCM CED and chromosomal damage were obtained. The 95% lower confidence bound of BMD of VCM CED was 2.86 mg/m(3) -year for both genders combined, leading to an estimated exposure limit of 0.072 mg/m(3) assuming a work life of 40 years. CONCLUSIONS: VCM exposure may induce chromosomal damage at occupational exposure levels below the Chinese national occupational health standard. Further research is needed to better understand micronuclei as biomarker of VCM genotoxicity. Better dose-response assessment and BMD estimation are desirable in order to improve the quantification of occupational exposure limits for VCM with respect to non-cancer risk.

DNA repair gene polymorphisms and micronucleus frequencies in Chinese workers exposed to vinyl chloride monomer.

Vinyl chloride monomer (VCM) is genotoxic and cancerogen agent. Individual variations in response to the exposure have been noticed and the variations may be due to genetic differences in the removal of VCM-DNA adducts, such as polymorphism in genes NER pathway and BER pathway. This study explores the relationship between genetic polymorphism of seven genes within the NER pathway (XPA, XPD, XPC, XPG, XPF, and ERCC1) and BER pathway (APE1), and susceptibility to chromosomal damage after exposure to VCM. One hundred and eighty workers occupationally exposed to VCM and 43 unexposed controls were investigated. Chromosome damage in peripheral lymphocytes was measured by the cytokinesis-blocked micronucleus assay. PCR-RFLP technique was applied to detect polymorphisms of the seven genes. The influence of genotype, age, gender, cumulative exposure dose, alcohol consumption, and smoking status on the frequencies of MN was determined using univariate and multiple Poisson regression analyses. We found XPA A23G variant workers had significantly higher MN frequencies than those from the wild-type homozygous counterparts (P = 0.01). Those with the variant XPD Lys751Gln genotype had marginally higher MN frequencies (P = 0.07). On the other hand, XPC PAT and XPF 5'-UTR T2063A variant workers had significantly lower MN frequencies compared with those from their wild-type homozygous counterparts (P = 0.04 and P = 0.004, respectively). Our findings suggest that XPC PAT, XPD Lys751Gln, XPA A23G and XPF 5'-UTR T2063A contribute to the level of chromosome damage in occupational exposure to VCM in Chinese population.

[Susceptibility of chromosomal damage among workers exposed to vinyl chloride monomer].

OBJECTIVE: To explore the association between chromosomal damage induced by vinyl chloride monomer (VCM) and polymorphisms of xenobiotic metabolism genes and DNA repair genes. METHODS: Cytokinesis-block micronucleus (CBMN) test was performed to detect chromosomal damage in peripheral lymphocytes of 402 VCM-exposed workers. Multiplex PCR was used to simultaneously amplify GSTM1 and GSTT1 genes, other genetic polymorphisms were performed using a PCR-RFLP technique. RESULTS: Multiple (adjusted) Poisson regression analysis showed that mean MN frequencies were significantly elevated for the intermediate (4000-40000 mg) and high (> 40000 mg) exposure groups as compared with the low exposure group (P = 0.003 and 0.03, respectively). For genetic polymorphisms, the exposed workers with CYP2E1 or XRCC1 Arg280His variance showed a higher CBMN frequency than their wild-type homozygous counterparts (P = 0.02); so did the workers with GSTP1 105Val/Val genotype or ALDH2 504Glu/Glu genotype than those with a combination of other genotypes (P = 0.01 and 0.003, respectively). CONCLUSION: Our findings reveal that cumulative exposure dose of VCM and common genetic variants in genes, such as GSTP1, CYP2E1, ALDH2, XRCC1 Arg280His genotypes, are the major factors that modulate MN induction in VCM- exposed workers. Further study to investigate the relationship between individual characteristics and genetic susceptibility to VCM-caused chromosome damage is warranted, it is helpful for us to understand the mechanism of VCM metabolism, to find the biomarkers of susceptibility and to recognize the susceptible individuals in the primary prevention of VCM-caused damage.

Genetic polymorphisms of XRCC1, HOGG1 and MGMT and micronucleus occurrence in Chinese vinyl chloride-exposed workers.

In this study, a group of 313 workers occupationally exposed to vinyl chloride monomer (VCM) and 141 normal unexposed referents were examined for chromosomal damage using the cytokinesis-blocked micronucleus (CBMN) assay in peripheral lymphocytes. We explored the relationship between genetic polymorphisms of XRCC1 (Arg194Trp, Arg280His and Arg399Gln), MGMT(Leu84Phe) and hOGG1 (Ser326Cys) and susceptibility of chromosomal damage induced by VCM. Polymerase chain reaction-restriction fragment length polymorphism techniques were used to detect polymorphisms in XRCC1, hOGG1 and MGMT. It was found that the micronuclei (MN) frequency of exposed workers (4.86 +/- 2.80) per thousand was higher than that of the control group (1.22 +/- 1.24) per thousand (P < 0.01). Increased susceptibility to chromosomal damage as evidenced by higher MN frequency was found in workers with hOGG1 326 Ser/Cys genotype [frequency ratio (FR) = 1.21, 95% confidence interval (CI): 1.02-1.46; P < 0.05], XRCC1 194 Arg/Trp (FR = 1.12, 95% CI: 1.00-1.25; P < 0.05) and XRCC1 280 Arg/His and His/His genotypes (FR = 1.12, 95% CI 1.00-1.26, P < 0.05). Moreover, among susceptibility diplotypes, CGA/CAG carriers had more risk of MN frequency compared with individuals with wild-type CGG/CGG (FR = 1.67, 95% CI: 1.19-2.23; P < 0.05). MN frequency also increased significantly with age in the exposed group (FR = 1.13, 95% CI: 1.00-1.28; P < 0.05). Thus, CB-MN was a sensitive index of early damage among VCM-exposed workers. Genotype XRCC1 Arg194Trp, Arg280His, hOGG1 Ser326Cys, diplotype CGA/CAG and higher age may have an impact on the chromosome damage induced by VCM.

Genetic polymorphisms in metabolizing enzymes and susceptibility of chromosomal damage induced by vinyl chloride monomer in a Chinese worker population.

OBJECTIVE: To evaluate whether polymorphisms in metabolizing enzymes contributed to susceptibility of chromosomal damage induced by vinyl chloride monomer (VCM). METHODS: Cytokinesis block micronucleus test was performed on 185 VCM-exposed workers and 41 control subjects to detect chromosomal damage in peripheral lymphocytes. The polymerase chain reaction and restriction fragment length polymorphism technique was applied to detect polymorphisms of GSTT1, GSTM1, GSTP1G/A, CYP2E1G/C, and CYP2D6G/C. Poisson regression analysis was performed. RESULTS: Sex, age, VCM exposure, GSTP1, and CYP2E1 genotype can influence chromosomal damage. There was a 1.51-fold increased micronucleus frequency for GSTP1GG genotypes individuals compared with those GSTP1AA/GA genotype individuals (P < 0.05), the effect of polymorphism in CYP2E1 gene was more pronounced for allele C compared with allele G (P < 0.05). CONCLUSIONS: Polymorphisms of GSTP1G/A and CYP2E1G/C, which are potential susceptibility biomarkers of chromosomal damage in VCM-exposed worker.

Prevalence and persistence of chromosomal damage and susceptible genotypes of metabolic and DNA repair genes in Chinese vinyl chloride-exposed workers.

Vinyl chloride (VC) was classified as a group 1 carcinogen by IARC in 1987. Although the relationship between VC exposure and liver cancer has been established, the mechanism of VC-related carcinogenesis remains largely unknown. Previous epidemiological studies have shown that VC exposure is associated with increased genotoxicity in humans. To explore chromosomal damage and its progression, and their association to genetic susceptibility, we investigated 402 workers exposed to VC, a 77 VC-exposed cohort and 141 unexposed subjects. We measured the frequencies of cytokinesis-block micronucleus (CBMN) to reflect chromosomal damage and conducted genotyping for six xenobiotic metabolisms and five DNA repair genes' polymorphism. Data indicate that 95% of the control workers had CBMN frequencies

[Sleep habits and sleep disturbance in school-age children of China].

OBJECTIVE: To survey the sleep habits (bedtime, wake time), sleep duration, and sleep problems in school-age children of China. METHOD: From November to December, 2005, a total of 19,299 school-age children from 55 elementary schools of 9 cities entered the study by a cross-sectional survey. A parent-administered questionnaire and the Chinese version of the Children's Sleep Habits Questionnaire were applied to investigate children's sociodemographic characteristics and sleep behaviors, respectively. RESULTS: The mean sleep duration was 9 hours and 10 minutes (9:10, SD:48 min) during the weekdays and 9:48 (SD: 63 min) during the weekends. In about 71.4% and 41.8% school-aged children the sleep duration per day did not reach the lowest criterion of 10 hours recommended by the Ministry of Education of China during weekdays and weekends, respectively. Sleep problems were common with prevalence ranging from 14.5% for sleep-disordered breathing to 75.3% for daytime sleepiness. Parasomnia (chi(2) = 13.76, P < 0.01) and sleep-disordered breathing (chi(2) = 119.83, P < 0.01) were more prevalent in boys than in girls; however, sleep anxiety was more prevalent in girls than in boys (chi(2) = 19.42, P < 0.01). Except for night waking, other types of sleep problems were significantly associated with age. CONCLUSIONS: Inadequate sleep duration and sleep problems prevail among school-age children, which indicates that children's sleep health may be a major public health concern in China.

Genetic polymorphisms, messenger RNA expression of p53, p21, and CCND1, and possible links with chromosomal aberrations in Chinese vinyl chloride-exposed workers.

This study explores the relationship between genetic polymorphisms of p53, p21, and CCND1, and the susceptibility of chromosomal damage induced by vinyl chloride monomer (CH(2)=CHCl, VCM). Besides gene polymorphisms, we detected the mRNA expression of p53, p21, and CCND1 in VCM-exposed workers and in a control group. One hundred and eighty-three workers occupationally exposed to VCM were investigated. Chromosome damage in peripheral lymphocyte was measured by cytokinesis-block micronucleus assay. The PCR-restriction fragment length polymorphism technique was applied to detect polymorphisms of p53, p21 (exon 2 and exon 3), and CCND1 genes (exon 4). The quantity of gene mRNA expression was detected by real-time PCR (SYBR Green I). Taking into account the effects of genetic polymorphisms, as well as demographic and habitual factors, Poisson regression analysis showed that the risk of chromosomal damage induced by VCM for individuals carrying the p53 intron 6 heterozygous and mutant homozygous genotype was 1.23 times larger (90% confidence interval, 1.01-1.51 P=0.0814), compared with those carrying wild-type homozygous genotypes. The p53 exon 4, intron 3, and intron 6 haplotype pairs of MMM/WWW (M, mutation allele; W, wild allele), and MWM/WWW were associated with increased frequencies of micronuclei. The p53 mRNA expression of VCM-exposed workers was significantly lower than that of nonexposed workers, but p21 mRNA expression in VCM-exposed workers was significantly higher than that of nonexposed workers. Our findings suggest that the p53 intron 6 polymorphism is one of the factors that potentially influence the frequency of micronuclei induced by VCM.

CYP2E1 mRNA expression, genetic polymorphisms in peripheral blood lymphocytes and liver abnormalities in Chinese VCM-exposed workers.

OBJECTIVE: To study the relationship between expression of cytochrome P4502E1 (CYP2E1) in human lymphocytes, variant CYP2E1 genotype, exposure to vinyl chloride monomer (VCM), and liver abnormalities in VCM-exposed workers. METHODS: A case-control study was performed on 90 male occupationally exposed workers and 42 matched male nonexposed controls. Data were collected based on health surveillance, workplace investigation and questionnaire Survey. Total RNA and DNA were isolated from peripheral blood lymphocytes, and CYP2E1 mRNA expression was determined using RT-PCR, and the presence of CYP2E1 polymorphisms was identified based on PCR-RFLP. RESULTS: The mRNA expression of CYP2E1 in exposed workers (0.89+/-0.46) was significantly higher than in nonexposed controls (0.61+/-0.35) (P < 0.01). Logistic regression analysis demonstrated a statistically significant association between CYP2E1 mRNA expression levels and liver abnormalities in the VCM-exposed workers (OR = 3.66, P < 0.05). The genotype frequency for CYP2E1 variants among VCM-exposed workers was not significantly different between workers with liver abnormalities and those without. CONCLUSIONS: Liver abnormalities in subjects exposed to VCM are positively associated with expression of peripheral blood lymphocyte mRNA, which is significantly increased in exposed workers compared to nonexposed controls. Therefore, CYP2E1 mRNA levels may be useful for health surveillance and protection of VCM-exposed workers.

[Polymorphisms of FAS and FASL genes and susceptibility of silicosis].

OBJECTIVE: To explore the relationship between polymorphisms of FAS and FASL genes and genetic susceptibility of silicosis. METHODS: A case-control study was conducted. The case group was 183 male patients with silicosis and the control group was 111 male silica-exposed but without silicosis miners. Data on total dust concentrations was collected to estimate cumulative total dust exposure (CTE) of each subject and each person's characteristics and work history were obtained from questionnaire. Polymerase chain reaction re-strained fragment length polymorphism technique (PCR-RFLP) was applied to detect the single nucleotide polymorphisms (SNPs) of FAS-1377, FAS-670 and FASL-844. Associations between polymorphisms and risk of silicosis and stages, interactions between polymorphisms, between polymorphisms and CTE and smoking and haplotypes were analyzed. RESULTS: There were no differences in the FAS-1377, FAS-670 and FASL-844 genotypes between the case group and the control group (P > 0.05). No association was observed between FAS-1377, FAS-670 and FASL-844 polymorphisms and silicosis and stages (P > 0.05). The frequencies of FAS-1377G/-670G haplotype in the cases (9.6%) were higher than those in the controls (3.6%) (P < 0.05). No interactions between the polymorphisms of different genes, the gene polymorphism and the total accumulative total dust, the gene polymorphism and smoking were observed (P > 0.05). CONCLUSION: FAS-1377, FAS-670 and FASL-844 polymorphisms are not susceptible factors of silicosis. The FAS-1377G/-670G haplotype might be a susceptibility marker of silicosis.