Study on fibrosis changes in the lungs of mice caused by repeated inhalation of polyhexamethyleneguaidine disinfectant / 中华预防医学杂志

To explore the lung damage caused by repeated inhalation of polyhexamethyleneguanidine (PHMG) disinfectant aerosol and the corresponding toxicological characteristics. Thirty four-week-old mice of C57BL/6N strain were randomly divided into three groups, the control group, low-dose group, and high-dose group. Each group had 5 male mice and 5 female mice. Lab II-level purified water was used in the control group. The PHMG disinfectant aerosol was generated by using the ultrasonic atomization of the aqueous solution containing PHMG. The PHMG concentrations in the low-and high-dose groups were 0.1 mg/ml (0.01%) and 1 mg/ml (0.1%), respectively. The concentration of PHMG in the post-chemical exposure room was 1.03 mg/m(3) and 9.09 mg/m(3) according to the air sampler analysis. The experimental mice were exposed to the PHMG in dynamic respiratory exposure mode for 4 hours every day in 21 days. After 21-day exposure, bronchia alveolus lung fluids (BALFs) were used to evaluate the inflammatory cells in the lungs, and pathological evaluation, special staining and immunohistochemical methods were further performed to evaluate the key indicators of pulmonary fibrosis. Compared to the control group, the body weight of mice in the high-dose group was significantly decreased (0.05), while that of mice in the low-dose group did not significantly differ (0.05). The number of inflammatory cells in BALFs of low-dose exposed mice was slightly reduced, and the lung tissue pathology began to show lung damage with early fibrosis symptoms (0.05). The pathological examination of mice in the high-dose group showed changes in pulmonary fibrosis. Immunohistochemical staining showed that pulmonary fibrosis marker, α-SMA, was significantly increased in low-dose group and high-dose group (0.05). The repeated inhalation of PHMG disinfectant could cause lung damage such as pulmonary fibrosis in mice. It could suggest that special warnings should be given to this common disinfectant and respiratory protection measures should be adopted during industrial production and daily use.

Association between polymorphisms of metabolic genes and telomere length in workers exposed to polycyclic aromatic hydrocarbon / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the association between the polymorphisms of metabolic genes and telomere length of genomic DNA in peripheral blood of workers exposed to polycyclic aromatic hydrocarbons (PAHs).</p><p><b>METHODS</b>One hundred and forty five coke-oven workers exposed to PAHs and sixty eight non-exposed medical staffs were recruited in this study. Urinary 1-hydroxypyrene (1-OHP) served as the internal exposure dose of PAHs for all subjects. Relative telomere length (RTL) of genomic DNA in peripheral blood was used as telomere length and measured by real-time PCR. Polymorphisms of metabolic genes were detected by PCR-based methods.</p><p><b>RESULTS</b>Compared with control group, the exposure group shown a decreased RTL (1.10 +/- 0.75 vs 1.43 +/- 1.06, P < 0.05). In the coke-oven workers, after adjusting the sex, age, cigarettes per day and urinary 1-OHP, RTL (1.25 +/- 0.93) of workers with CT genotype at the CYP1A1 3801 T > C was significantly longer than that (0.93 +/- 0.51) of workers with TT genotype (P < 0.05). RTL (0.90 +/- 0.58) of individuals with the Tyr/His genotype at mEH Tyr113His was significantly shorter than that (1.24 +/- 0.90) of individuals with the Tyr/Tyr genotype (P < 0.05). RTL (1.02 +/- 0.64) of individuals with the CT genotype at AHR rs10250822 was significantly shorter than that (1.36 +/- 1.14) of individuals with the CC genotype (P < 0.05). RTL (0.93 +/- 0.54) of individuals with the AT genotype at AHR rs10247158 was significantly shorter than that (1.19 +/- 0.84) of individuals with the AA genotype (P < 0.05).</p><p><b>CONCLUSION</b>The results of present study suggested that PAHs exposure could induce the shorted RTL, CYP1A1, mEH, AHR polymorphisms might influence the change of telomere length of genomic DNA in peripheral blood of workers exposed to PAHs.</p>

Association between telomere length and occupational polycyclic aromatic hydrocarbons exposure / 中华预防医学杂志

<p><b>OBJECTIVE</b>To explore the association between polycyclic aromatic hydrocarbons (PAHs) exposure and telomere length (TL), so as to investigate the effective biomarkers to evaluate the genetic damage in peripheral blood of workers exposed to PAHs.</p><p><b>METHODS</b>The exposure group consisted of 145 coke-oven workers (including 30 top-oven workers, 76 side-oven workers and 39 bottom-oven workers), and the non-exposure control group comprised 68 medical staffs. At 6 hours after the weekend duty shift, the samples of urine and 1 ml venous blood were collected from each subject. Airborne benzene-soluble matter (BSM) and particulate-phase B(a)P in the working environment of coke-oven and controls were sampled and analyzed. The concentration of urinary 1-hydroxypyrene (1-OHPyr) was determined. A real-time PCR method was used to determine the relative telomere length (RTL) of genomic DNA in peripheral blood. The relationship between the RTL and external exposure of PAHs, the potential factors which might have influence on TL were analyzed.</p><p><b>RESULTS</b>The medians of air BSM and particulate-phase B(a)P were higher in coke-oven (BSM: 328.6 µg/m(3); B(a)P: 926.9 ng/m(3)) than those in control working environment (BSM:97.8 µg/m(3); B(a)P: 49.1 ng/m(3)). The level of 1-OHPyr among coke-oven workers was significantly higher than that of non-exposed group (12.2 µmol/mol Cr vs 0.7 µmol/mol Cr; t = 26.971, P < 0.01). RTL in coke-oven workers were significantly shorter than those of controls (1.10 ± 0.75 vs 1.43 ± 1.06; t = 2.263, P = 0.026), and after adjusting for cigarettes per day and urinary 1-OHPyr, the significant difference was still observed (F(adju) = 5.496, P(adju) = 0.020). Stratification analysis found that RTL among the male and non-drinking groups in coke-oven workers were shorter than those the same sex and alcohol using status in controls (1.08 ± 0.73 vs 1.51 ± 1.10, F = 9.212, P = 0.003; 0.96 ± 0.38 vs 1.26 ± 0.46, F = 6.484, P = 0.012). Significant correlation between RTL and age was found (r = -0.284, P = 0.019) in non-exposure group.</p><p><b>CONCLUSION</b>PAH-exposure has effect on TL of genomic DNA in peripheral blood, which is mainly observed in the male and non-drinking groups between PAH-exposed workers and controls. It indicates that TL of genomic DNA in peripheral blood might be an effective biomarker as PAH-induced genetic damage.</p>

Mutagen sensitivity in peripheral blood lymphocytes among coke-oven workers / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate the sensitivity to bleomycin (BLM) in peripheral blood lymphocytes (PBL) among coke-oven workers.</p><p><b>METHODS</b>Ninty-four coke-oven workers with exposure to a high level of polycyclic aromatic hydrocarbons and 64 non-coke-oven workers (control) were recruited into this study. PBL was challenged by 8 microg/ml BLM, a known carcinogen, to induce certain amount of DNA damage, the difference of olive tail moment (TM) measured by comet assay before and after BLM treatment reflected the sensitivity towards mutagens.</p><p><b>RESULTS</b>The distribution of age, sex, and prevalence of smoking and drinking were not significantly different between these two groups. The geometric mean of urinary 1-hydroxypyrene (1-OHP) was significantly higher in coke-oven workers than in controls (9.0 versus 1.5 microg/L, t = -9.317, P < 0.01). The coke-oven workers showed significantly higher sensitivity to BLM than controls (17.7 versus 14.9, t = -2.583, P = 0.01). A large inter-group difference in sensitivity to BLM was observed in both controls and coke-oven workers. Stratification analysis revealed the significant association between high 1-OHP level (> 9.0 microg/L) and increased sensitivity to BLM (F = 4.001, P = 0.05) among coke-oven workers. Smoking subjects showed a significant higher value of sensitivity than nonsmokers in controls but not in coke-oven workers. No significant difference was observed between age, drinking status, coking history or external exposure class and BLM sensitivity.</p><p><b>CONCLUSION</b>Exposure to coke oven emission could increase the sensitivity to mutagens, which might be a reason of high incidence of lung cancer among coke-oven workers.</p>

Association between polycyclic aromatic hydrocarbons exposure levels and nucleoplasmic bridge and nuclear bud frequencies in coke-oven workers / 中华预防医学杂志

<p><b>OBJECTIVE</b>To seek new effect biomarkers as to evaluating the chromosomal damage in peripheral blood lymphocytes in coke-oven workers who were exposed to polycyclic aromatic hydrocarbons (PAHs).</p><p><b>METHODS</b>One hundred and fifty-eight coke-oven workers and 69 controls were recruited in this study. Nucleoplasmic bridges and nuclear buds were counted as indicators of chromosomal damage in terms of cytokinesis-block micronucleus (CBMN) test. Occupational history, age, sex, smoking and alcohol using status of all subjects were collected by questionnaire.</p><p><b>RESULTS</b>Frequencies of nucleoplasmic bridge in coke-oven workers were (9.41 +/- 3.73)% per hundred, and the frequencies of nuclear buds were (7.13 +/- 4.01)% per hundred, which were significantly higher (P < 0.01) than those of controls (1.88 +/- 1.49)% per hundred and (2.20 +/- 1.73)% per hundred respectively. The dose-effect relationships between nucleoplasmic bridges or nuclear buds and PAHs exposure levels were identified. Compared with male coke-oven workers, female workers had less nucleoplasmic bridges or nuclear buds. No effects of age, smoking and alcohol using were found on nucleoplasmic bridges or nuclear buds among coke-oven workers.</p><p><b>CONCLUSION</b>Nucleoplasmic bridges and nuclear buds might be effect biomarkers in coke-oven workers.</p>

Association between nucleotide excision repair gene polymorphisms and chromosomal damage in coke-oven workers / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate the association of polymorphisms of nucleotide excision repair genes and chromosomal damage in peripheral blood lymphocytes among coke-oven workers.</p><p><b>METHODS</b>The genotypes of ERCC1 C19007T, ERCC2 C22541A, ERCC2 G23591A, ERCC2 A35931C, ERCC4 T30028C, ERCC5 G3507C and ERCC6 A3368G among 140 coke-oven workers and 66 non-coke-oven controls were determined by PCR-PFLP methods. Chromosomal damage was detected by cytokinesis-block micronucleus (CBMN) assay.</p><p><b>RESULTS</b>Multivariate analysis of covariance revealed that in coke-oven workers, the ERCC1 19007 CC genotype exhibited significantly higher CBMN frequency [(1.05 +/- 0.68)%] than did the CT [(0.81 +/- 0.66)%] (P = 0.01) or TT [(0.66 +/- 0.37)%] (P = 0.05) or CT + TT genotypes [(0.75 +/- 0.63)%] (P = 0.004). For the ERCC6 A3368G polymorphism, AA genotype exhibited significantly higher CBMN frequency [(1.00 +/- 0.69)%] than did the AG [(0.67 +/- 0.42)%] (P = 0.05) or AG + GG genotypes [(0.66 +/- 0.41)%] (P = 0.02). Stratification analysis found the significant association between the two polymorphisms, ERCC1 C19007T and ERCC6 A3368G, and the CBMN frequencies were most pronounced in older workers. In addition, for the polymorphism of ERCC2 G23591A, GA carriers had significantly higher CBMN frequencies [(1.40 +/- 0.63)%] than those GG carriers [(0.98 +/- 0.59)%] (P = 0.01) in older workers.</p><p><b>CONCLUSIONS</b>Our results suggested that polymorphisms of ERCC1 C19007T, ERCC6 A3368G and ERCC2 G23591A were associated with the CBMN frequencies in coke-oven workers.</p>

Immunological mechanism in development of allergic dermatitis in guinea pig induced by trichloroethylene in vitro / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the immunological mechanism of allergic dermatitis induced by trichloroethylene (TCE).</p><p><b>METHODS</b>The guinea pig model of TCE-induced allergic dermatitis was established by Guinea pig Maximization Test. The effects of TCE and its metabolites on splenic lymphocytes of TCE-sensitized and non-sensitized guinea pig were detected by MTT assay.</p><p><b>RESULTS</b>For TCE-sensitized guinea pig, the survival rate of lymphocytes cultured with TCE (+S9) was significantly higher than that cultured with TCE (-S9) (83.0% +/- 3.4% vs 75.9% +/- 7.9%, P < 0.01), while, for normal animals, the survival rate of lymphocytes cultured with TCE (+S9) was significantly lower than that cultured with TCE (-S9) (63.4% +/- 8.4% vs 77.0% +/- 7.2%, P < 0.01). The survival rate of lymphocytes cultured with TCE (+S9) in TCE-sensitized animals was higher than that in normal animals (83.0% +/- 3.4% vs 63.4% +/- 8.4%, P < 0.05), but no statistically significant difference was found for TCE (-S9) (75.9% +/- 7.9% vs 77.0% +/- 7.2%, P > 0.05).</p><p><b>CONCLUSION</b>Cytotoxicity of TCE to normal lymphocytes and proliferation of sensitized lymphocytes were enhanced by metabolic activation. The metabolites of TCE may act as effective immune hapten to stimulate the proliferation of hapten-specific lymphocytes in TCE-sensitized animals.</p>

Association of XRCC1 polymorphisms and chromosomal damage levels in coke-oven workers / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate the association of XRCC1 polymorphisms and chromosomal damage levels in peripheral blood lymphocyte in coke-oven workers.</p><p><b>METHODS</b>The study included 141 coke-oven workers who exposed to a high level of polycyclic aromahaplotpetic hydrocarbon and 66 non-exposed controls. Urinary 1-hydroxypyrene and chromosome damage in peripheral lymphocyte were measured. Four -tagging single nucleotide polymorphisms in XRCC1 gene, including C26304T, G27466A, G28152A and G36189A, were detected and the XRCC1 haplotypes were estimated by using an extension of Clark algorithm. The associations between haplotype pairs and micronuclei data were assessed by analysis of covariance in the exposed and non-exposed groups.</p><p><b>RESULTS</b>The geometric means of urinary 1-hydroxypyrene levels in coke-oven workers and the controls were 12.0 and 0.7 micromol/mol Cr respectively (P < 0.01). The cytokinesis-block micronucleus cytokinesis-block micronucleus frequencies (number of micronucleus per 1 000 binucleated lymphocytes) was significantly higher in coke-oven workers (0.95 +/- 0.66)% than in the controls (0.40 +/- 0.36)%, P < 0.01. The haplotype CGGG was associated with the decreased frequencies of total micronucleus, and the haplotypes TGGG (P = 0.01) and CGAG (P < 0.05) were associated with the increased frequencies of total micronucleus in the multivariate analysis with adjustment for covariates among coke-oven workers.</p><p><b>CONCLUSIONS</b>The genetic polymorphisms of XRCC1 gene could influence the chromosome damage levels in coke-oven workers.</p>

Association of metabolic and DNA repair enzyme gene polymorphisms and DNA damage in coke-oven workers / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate the association of polymorphisms of metabolic and DNA repair enzyme genes and DNA damage in peripheral blood lymphocytes in coke-oven workers.</p><p><b>METHODS</b>One hundred and forty-four coke-oven workers and 50 controls were recruited in this study. Urinary 1-hydroxypyrene (1-OHP) levels were measured as the internal dose of polycyclic aromatic hydrocarbons exposure. DNA damage was detected by alkaline comet assay, and the value of 1.74 was used as the cut-off value to determine whether the individual's DNA damage was positive. The genotypes of CYP1A1, CYP2E1, GSTP1, NQO1, mEH and XRCC1 were determined by PCR-based methods. With adjustment for urinary 1-OHP, age, sex, multiple analysis of covariance was used to study the association between genotypes and the ln-transformed olive TM and multiple logistic regression was used to calculate the adjusted OR and the 95% CI for the risk of DNA damage.</p><p><b>RESULTS</b>In 144 coke-oven workers, with adjustment for urinary 1-OHP, coking history and sex, the olive TM was significantly higher with XRCC1 280His allele than those with Arg allele (5.6 vs. 2.8, P < 0.01). The subjects with XRCC1 280His allele also have significantly higher risk for DNA damage than subjects with Arg allele (adjusted OR = 2.66, 95% CI = 1.00-7.14, P = 0.05) and the subjects with GSTP1 104Val allele have higher risk for DNA damage than subjects with Ile allele (adjusted OR = 1.90, 95% CI = 0.94-3.85, P = 0.07).</p><p><b>CONCLUSION</b>XRCC1 and GSTP1 polymorphisms might influence the susceptibility of DNA damage in occupational PAH-exposed coke-oven workers.</p>

Early genetic effects on workers occupationally exposed to formaldehyde / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate the DNA and chromosome damage in peripheral blood lymphocyte of workers occupationally exposed to formaldehyde (FA).</p><p><b>METHODS</b>All 151 workers occupationally exposed to FA from two plywood factories and 112 workers without occupational FA exposure working in a machine manufactory were recruited into this study. Comet assay and cytokinesis-block micronucleus technique was used to evaluate the DNA and chromosomal damage of peripheral blood lymphocyte. The air FA samples were collected with SKC 224-PCXR8 air samplers. Gas chromatography was used to analyze the FA level. Personal information including occupational history, age, sex, smoking and drinking status was collected by the questionnaire.</p><p><b>RESULTS</b>The time weighted average concentration (TWA) of FA in the working environment of FA-exposed workers (range 0.10 - 7.88 mg/m(3)) was higher than those in controls (< 0.01 mg/m(3)). The olive tail moment (Olive TM) in low FA-exposed workers [3.03 (2.49 - 3.67)] was lower than that in high FA-exposed workers [3.95 (3.53 - 4.43)], but higher than that in controls [0.93 (0.78 - 1.10)], the differences were statistical significant (P < 0.05). Comet trail length in FA-exposed workers were significantly higher than that in controls [6.78 (6.05 - 7.60)], but no significant differences ware found between the high FA-exposed workers [12.59 (11.80 - 13.43)] and the low FA-exposed workers [11.25 (10.12 - 12.50)]. The frequency of micronuclei per 100 binucleated cells in low FA-exposed workers (0.41 +/- 0.25) was lower than that in high FA-exposed workers (0.65 +/- 0.36), but higher than that in controls (0.27 +/- 0.13), the differences were statistical significant (P < 0.05). The increased tendencies with the exposure levels were found in those three indices. In stratification analysis, the same results were found.</p><p><b>CONCLUSION</b>In the current FA exposure levels, the DNA and chromosomal damage in peripheral blood lymphocyte might be induced by FA exposure, and be increased with the levels of exposure.</p>

Genetic damage in peripheral blood lymphocyte of coke oven workers / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate DNA and chromosome damage in peripheral blood lymphocyte of coke oven workers exposed to polycyclic aromatic hydrocarbons (PAHs).</p><p><b>METHODS</b>One hundred and thirty-seven coke oven workers and 50 controls without occupational PAHs exposure were investigated. Comet assay and cytokinesis-block micronucleus (CBMN) detection were used to evaluate DNA and chromosomal damage levels in peripheral blood lymphocyte. Urinary 1-hydroxypyrene level was used to assess the personal internal PAHs exposure dose. Personal information including occupational history, age, sex, smoking and drinking status was collected by questionnaire.</p><p><b>RESULTS</b>Urinary 1-hydroxypyrene level in coke oven workers [(5.76 +/- 1.04) micro mol/mol Cr] was significantly higher than that in controls [(0.70 +/- 0.32) micro mol/mol Cr]. The rate of CBMN and comet tail moment of lymphocyte in coke oven workers [8.0 per thousand (0.0 per thousand - 30.0 per thousand ) and 2.09 (0.31 - 75.41), respectively] were higher than those in controls [3.5 per thousand (0.0 per thousand - 13.0 per thousand ) and 1.05 (0.11 - 6.63), P < 0.05]. In controls, the comet moment in smokers was significantly higher than that in non-smokers [1.44 (0.23 - 6.63) vs 0.81 (0.11 - 3.47), P < 0.05]. According to the length of work, 137 coke oven workers were classified into 3 groups i.e. 0.5 yrs , 16.0 yrs and 22.0 yrs group, and the comet moments were 1.34 (0.31 - 37.84), 2.32 (0.49 - 52.97) and 3.20 (0.45 - 75.41) respectively after adjusting the age, sex, smoking, drinking and level of urinary 1-hydroxy-pyrene. There was a rising tendency along with the increase in length of work.</p><p><b>CONCLUSION</b>Under present PAHs exposure levels, both comet assay and Cytokinesis-block micronucleus test could detect PAHs-induced genotoxicity in coke oven workers, and comet assay is more suitable to assess the cumulative damage effect on DNA.</p>

Associations between genetic polymorphisms of glutathione S-transferase M1 and T1, smoking and susceptibility to colorectal cancer: a case-control study / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the associations between genetic polymorphisms of glutathione S-transferase M1 and T1 (GSTM1 and GSTT1), smoking and susceptibility to colorectal cancer.</p><p><b>METHODS</b>A case-control study of 126 patients and 343 healthy controls was conducted to investigate the role of GSTM1 and GSTT1 polymorphisms in colorectal cancer. Genotypes of GSTM1 and GSTT1 polymorphisms were analyzed by multiplex allele-specific polymerase chain reaction (PCR).</p><p><b>RESULTS</b>The frequencies of GSTM1 null and GSTT1 null genotypes were 55.5% and 20.4%, respectively. After adjustment for age and sex, among those with GSTT1 null genotype, the GSTM1 null genotype had a significant increased risk of rectal cancers compared to GSTM1 non-null genotype (OR=9.74, 95% CI, 1.13 - 83.85). A 2.22-fold risk of colon cancers was associated with GSTM1 null genotype compared to GSTM1 non-null genotype among current smokers (P >0.05). Individuals with GSTT1 null genotype and currently smoking had a significant risk of colon cancers (OR = 4.55, 95% CI, 1.14 - 18.17), and rectal cancers (OR = 4.60, 95% CI, 1.11 - 19.11).</p><p><b>CONCLUSION</b>This study suggests that certain null GSTM1 and GSTT1 genotypes may be associated with an elevated risk of colorectal cancer which may be modified by interaction of the two genetic polymorphisms and cigarette smoking.</p>

Preliminary study on naphthalene-metabolites-albumin adduct as an exposure biomarker for coke oven workers / 中华预防医学杂志

<p><b>OBJECTIVE</b>To study albumin adduct with naphthalene metabolites, namely 1,2-naphthoquinone (1,2-NPQ) and 1,4-naphthoquinone (1,4-NPQ), as a potential biomarker for intermediate/long-term exposure to polycyclic aromatic hydrocarbons (PAH) in coke oven workers.</p><p><b>METHODS</b>Twenty-eight coke oven workers and 22 control workers were recruited from a cokery. Spot urine and venous blood samples were collected from the workers after four continuously working days and personal information was obtained by questionnaire. Plasma albumin adduct was detected with gas chromatography-mass spectrometry.</p><p><b>RESULTS</b>Albumin adduct with 1,2- & 1,4-NPQ (1,2-NPQ and 1,4-NPQ), respectively, were detected in all coke oven workers and controls. Median plasma level of 1,2-NPQ-Alb in coke oven workers was significantly higher than that in controls (76.6 pmol/g vs. 44.9 pmol/g, P < 0.01). However, there was no significant difference in plasma median level of 1,4-NPQ-Alb between the two groups (48.6 pmol/g vs. 44.2 pmol/g, P > 0.05). Plasma level of 1,2-NPQ-Alb was significantly higher than that of 1,4-NPQ-Alb in coke oven workers. Urine levels of naphthalene, 1-naphthol, 2-naphthol and 1-pyrenol in coke oven workers correlated significantly with their plasma level of 1,2-NPQ-Alb (Pearson coefficient of correlation greater than 0.371, P < 0.01), but did not do significantly with 1,4-NPQ-Alb.</p><p><b>CONCLUSION</b>Plasma level of 1,2-NPQ-Alb could effectively reflect their magnitude of personal internal dose of exposure to air PAH, so it could be used as a potential biomarker to evaluate their intermediate/long-term exposure to PAH in coke oven workers.</p>

A study on the inherited susceptibility of chromosomal damage in peripheral blood lymphocytes among coke oven workers / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate the association between polymorphisms of metabolic enzyme genes and chromosomal damage risk in peripheral blood lymphocytes among coke oven workers.</p><p><b>METHODS</b>One hundred and fourty-nine coke oven workers and 24 referents without occupational polycyclic aromatic hydrocarbons (PAH) exposure were recruited in this study. Urinary 1-hydroxypyrene levels were measured as the internal dose of PAH exposure. The 6 per 1 000 of micronucleus value was used as the cut-off value to determine whether the individual's chromosomal damage was positive. The genotypes of CYP1A1, GSTM1, GSTT1, GSTP1, CYP2E1, NQO1, NAT2 and mEH genes were determined by PCR-based methods. Multiple logistic regression was used to calculate the adjusted ORs and the 95% CI for the risk of chromosomal damage and to analyze the gene-gene interaction.</p><p><b>RESULTS</b>In 173 subjects, after adjusting the occupational exposure, age, sex, smoking and drinking status, the subjects with GSTM1 null genotype have significantly higher risk for chromosomal damage than subjects with GSTM1 positive genotype (adjusted OR = 2.01, 95% CI = 1.03 -3.91). Compared with the wild homozygotes at P187S site of NQO1 gene, the variant homozygotes have significantly higher risk for chromosomal damage (adjusted OR = 3.18, 95% CI = 1.18 - 8.62). The subjects with variant allele at H113Y site of mEH gene have significantly lower risk for chromosomal damage (adjusted OR = 0.40, 95% CI = 0.19 - 0.88). No significant associations were found for other gene polymorphisms and chromosomal damage risk. In addition, the gene-gene interactions were also found among GSTM1, NQO1 gene P187S and mEH gene H113Y polymorphisms for the risk of chromosomal damage risk.</p><p><b>CONCLUSION</b>Significant associations between genetic polymorphisms in GSTM1, NQO1 and mEH gene and risk for chromosomal damage were found among occupational PAH-exposed workers, which related to the mechanism of PAH carcinogenesis.</p>

Effect of genetic polymorphisms of microsomal epoxide hydrolase on urinary 1-hydroxypyrene levels in coke oven workers / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the associations of polymorphisms of metabolic enzyme genes with urinary 1-hydroxypyrene levels in coke oven workers.</p><p><b>METHODS</b>One hundred and forty-eight workers from a coke oven plant and 69 controls without occupational PAHs exposure were selected in this study. Urinary 1-hydroxypyrene was detected by high performance liquid chromatography with florescence detector. The genotypes at I462V site in exon 7 of CYP1A1 gene, GSTM1, GSTT1, I105V site in GSTP1gene, Pst1 and Dra1 sites in CYP2E1 gene, P187S site in NQO1 gene, Kpn1, BamH1 and Taq1 sites in NAT2 gene, and H113Y, R139H sites in mEH gene were determined by PCR-based methods. Personal information including occupational exposure history, age, sex, smoking and drinking status was collected by the questionnaire.</p><p><b>RESULTS</b>The level of urinary 1-hydroxypyrene in coke oven workers [(5.61 +/- 1.04) mol/mol Cr] was higher than that in control [(0.74 +/- 0.32) micro mol/mol Cr]. After adjusting external occupational exposure category and smoking, coke oven workers with variant homozygotes at H113Y site of mEH gene had significantly higher urinary 1-hydroxypyrene concentrations than those with heterozygotes, and wild homozygotes (6.41 +/- 1.09 vs. 6.24 +/- 1.08, and 4.62 +/- 0.95 micro mol/mol Cr, P < 0.05), and gene-gene interaction was found between CYP1A1 and mEH.</p><p><b>CONCLUSION</b>Genetic polymorphism of mEH gene could be a susceptible biomarker in coke oven workers which was involved in the individual susceptibility on metabolism of PAHs.</p>

Relationship of polycyclic aromatic hydrocarbon exposure with peripheral blood lymphocyte DNA damage in coke oven workers / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the relationship between lymphocyte DNA damage and polycyclic aromatic hydrocarbons (PAHs) exposure in coke oven workers.</p><p><b>METHODS</b>Two hundred and thirty-five coke oven workers and 30 controls were selected in this study. Alkaline single-cell gel electrophoresis was used to evaluate the lymphocyte DNA damage, HPLC was employed to measure 1-hydroxypyrene levels in spot urine samples which were obtained at the end of a workweek (4 days of 8 hours/day) and personal information including occupational exposure, age, sex, smoking and drinking status was collected by the questionnaire.</p><p><b>RESULTS</b>The lymphocyte DNA damage level expressed as olive moment in coke oven workers was significantly higher than that of controls [2.47 (0.22 approximately 46.68) vs 0.94 (0.42 approximately 4.21), P < 0.01], and correlation between urinary 1-hydroxypyrene concentrations and olive moment was found (Spearman Partial correlation coefficient = 0.22, P < 0.01) in coke oven workers. The 1.9 of olive moment value was used as the limit to determine whether the subject DNA damage was positive. The coke oven workers had significantly higher risk in DNA damage (adjusted OR = 5.38, 95% CI = 2.07 approximately 14.08) than did controls, and dose-response relationships were also found between external exposure (exposure category) or internal doses (urinary 1-hydroxypyrene) and DNA damage.</p><p><b>CONCLUSION</b>There are dose-effect and dose-response relationships between PAHs exposure and lymphocyte DNA damage in coke oven workers.</p>

Genetic susceptibility to intermediate myasthenia syndrome following organophosphate insecticides poisoning / 中华预防医学杂志

<p><b>OBJECTIVE</b>To explore the association of gene polymorphism of organophosphate insecticides (OPs) metabolic enzymes with intermediate myasthenia syndrome (IMS) following acute OPs poisoning.</p><p><b>METHODS</b>Thirty six of 147 acute OPs poisoning patients developed IMS one to four days after poisoning. Peripheral blood samples were collected from all the patients and whole blood cholinesterase (ChE) activity was determined by DTNB spectrometry. The genetic polymorphism of CYP2E1 (1091C-->T) and GSTP1 (313A-->G) were analyzed by polymerase chain reaction (PCR)-restrict fragment length polymorphism, CYP1A1 (4889A-->G), GSTM1 and GSTT1 by allele-specific PCR, and PON1 at 55 codon (55L-->M) by PCR-single strand conformation polymorphism.</p><p><b>RESULTS</b>The whole blood ChE activity in IMS patients was not significantly different from non-IMS patients at admission (38.22 +/- 17.56)% and (42.49 +/- 16.23)%, respectively, P > 0.05, but recovered much slower in IMS patients than that in non-IMS patients. The frequencies of heterozygote and variant homozygote of PON1 at 55 codon, GSTM1 null, and both GSTM1 and GSTT1 null were higher in IMS patients than those in non-IMS patients (P < 0.05), with odds ratios and their 95% confident intervals of 2.48 (1.06 - 5.78), 11.23 (2.95- 42.76), 2.53 (1.14 - 5.61) and 2.68 (1.20 - 5.97), respectively.</p><p><b>CONCLUSIONS</b>Patients of OPs and its mixture poisoning with genotype of variant allele at 55 codon of PON1, GSTM1 null and both GSTM1 and GSTT1 null probably had higher risk for IMS.</p>

A study on the relationship between urinary 1-hydroxypyrene level and early genetic effect among coke oven workers / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate the relationship between the urinary 1-hydroxypyrene level and cytokinesis-block micronucleus and the olive moment of comet assay in peripheral blood lymphocyte in coke oven workers.</p><p><b>METHODS</b>One hundred and thirty-three workers from a coke plant and 28 referents without occupational PAH exposure were recruited in this study. Urinary level of 1-hydroxypyrene was measured by alkaline hydrolysis combined with high performance liquid chromatography as an internal exposure dose, and the DNA and chromosomal damage of peripheral blood lymphocyte were evaluated with comet assay and cytokinesis-block micronucleus method. Personal information including occupational history, age, sex, smoking and alcohol drinking, was collected by questionnaire.</p><p><b>RESULTS</b>There existed a good correlationship between the urinary level of 1-hydroxypyrene and frequency of micronuclei per 1 000 binucleated cells or the olive moment of comet assay in the study subjects, after adjusting for sex, age, smoking and alcohol drinking (r > 0.25, P < 0.01). One hundred and sixty-one subjects were divided into three groups by their urine 1-hydroxypyrene level (expressed as 0.30 - 2.44, 2.45 - 7.09 and 7.10 - 33.10 micro mol/mol Cr), and the geometric means of their urinary levels of 1-hydroxypyrene were 1.14, 4.32 and 12.49 micro mol/mol Cr, respectively. After adjusting for age, sex, smoking and alcohol drinking by multiple nonparametric analysis of covariance, the median of olive moment of comet assay in the group of 7.10 - 33.10 micro mol/mol Cr was 3.67, significantly higher than that in the groups of 0.30 - 2.44 and 2.45 - 7.09; and the micronuclei frequencies in the groups of 2.45 - 7.09 and 7.10 - 33.10 micro mol/mol Cr were 8.00 per thousand and 7.50 per thousand, respectively, significantly higher than that in the group of 0.30 - 2.44 micro mol/mol Cr (6.00 per thousand ).</p><p><b>CONCLUSIONS</b>The comet assay of peripheral blood lymphocyte was more suitable to detect the PAHs-induced early genotoxicity, than the cytokinesis-block micronucleus.</p>