[The effect of 2,5-hexanedione on nerve growth factor in sciatic nerve of rats and VSC4.1 cell].

OBJECTIVE: To explore the effect of 2,5-hexanedione (2,5-HD) on the levels of nerve growth factor (NGF) in sciatic nerve of rats and motor-neurons. METHOD: A total of 50 Wistar rats were randomly designed into five groups and intoxicated with 400 mgxkg(-1)xd(-1) 2,5-HD for 0, 7, 14, 21, 28 d. Immunohistochemistry and real-time PCR were used to detect the levels of NGF and NGF mRNA. Motor neuron VSC4.1 cells were administrated with 0, 2.5, 5.0, 10.0, 20.0 mmol/L 2,5-HD for 24 h and 10.0 mmol/L 2,5-HD was chosen to intoxicated VSC4.1 cells for 0, 1, 3, 6, 12, 24, 48 h respectively. Immunofluorescence technique was selected to detect the levels of NGF. RESULTS: The NGF level in sciatic nerve of rats administrated with 400 mgxkg(-1)xd(-1) 2,5-HD showed increase tendency at begin and then decrease after exposure. The NGF mRNA level in 14 d (2(-DeltaDeltaCt)= 3.46), 21 d (2(-DeltaDeltaCt)= 5.28) and 28 d (2(-DeltaDeltaCt)= 3.10) were higher than those in 0 d (2(-DeltaDeltaCt)= 1) and 7 d (2(-DeltaDeltaCt)= 0.78). In vitro tests of VSC4.1 cells showed that NGF levels in 5.0 mmol/L (43.24 +/- 7.52), 10.0 mmol/L (43.48 +/- 10.86) and 20.0 mmol/L (63.13 +/- 10.68) were higher than those in 0 mmol/L (16.32 +/- 4.20)(q values were 19.92, 19.72, 32.78, respectively, P < 0.01) and 2.5 mmol/L (19.78 +/- 2.66) (q values were 17.50, 17.42, 30.63, respectively, P < 0.01) in 24 h and the NGF level in 20.0 mmol/L was higher than those in 5.0 mmol/L (q = 13.04, P < 0.01) and 10.0 mmol/L (q = 11.71, P < 0.01). The NGF levels of VSC4.1 cells with 10.0 mmol/L 2,5-HD in 6 h (18.66 +/- 2.89), 12 h (23.14 +/- 6.08), 24 h (27.66 +/- 6.11) and 48 h (17.25 +/- 3.05) were increased compared with that in 0 h (10.18 +/- 1.81) (q values were 9.64, 15.74, 21.76, 8.50, respectively, P < 0.01), 1 h (9.31 +/- 1.28) (q values were 10.28, 16.17, 21.95, 9.20, respectively, P < 0.01) and 3 h (10.44 +/- 2.13) (q values were 9.25, 15.24, 21.17, 8.10, respectively, P < 0.01), and NGF levels in 12 h and 24 h increased compared with those in 6 h (q values were 5.24, 10.77, respectively, P < 0.01) and 48 h (q values were 7.31, 13.26, respectively, P < 0.01). CONCLUSION: 2,5-HD could increase NGF levels in sciatic nerve of rats and motor-neurons, and the dose or time dependent effects were observed in this study.

[Effect of 2, 5-hexanedione on calcium homeostasis of motor neuron].

OBJECTIVE: To explore the mechanism of cytotoxic effect of 2, 5-hexanedione (2, 5-HD) on motor neuron. METHODS: Vsc4.1 (a cell line from motor neuron) was incubated with a series concentration of 2, 5-HD. The cell viability, Ca(2+) Mg(2+) ATPase and Na(+)K(+) ATPase were detected. Laser scanning confocal microscope (LSCM) was used for detecting intracellular calcium level. The average calcium level in VSC4.1 was measured by flow cytometry. RESULTS: The cell viability was decreased when Vsc4.1 cells were treated with 2, 5-HD at the dosage of 2.5, 5.0, 7.5, 10, 15 and 20 mmol/L for 24 hours. Compared with the control group the activity of Ca(2+) Mg(2+) ATPase was decreased to 70.02%, 77.44% and 47.47% respectively; the activity of Na(+)K(+) ATPase was decreased to 82.07%, 72.45% and 50.71%. The difference was significant. Intracellular free calcium of VSC4.1 cell was increased rapidly within 10 s and then recovered within 40 seconds when it was exposed to 33.5 mmol/L 2, 5-HD. An increase in intracellular calcium was observed when the VSC4.1 was treated with 33.5 mmol/L 2, 5-HD. The peak of intracellular calcium level occurred ten minutes later. CONCLUSION: The disturbance of calcium homeostasis may be involved in the mechanisms of neurotoxicity of 2, 5-HD.

[Association between XRCC1 gene polymorphisms and DNA damage of workers exposed to formaldehyde].

OBJECTIVE: To investigate the association between polymorphisms of DNA repair gene XRCC1 and DNA damage in peripheral blood lymphocytes among workers exposed to formaldehyde. METHODS: One hundred and fifty-one workers exposed to formaldehyde from plywood factories and one hundred and twelve workers without occupational exposure to formaldehyde were recruited into this study. DNA damage levels were measured by comet assay. The polymorphisms of XRCC1 gene were analyzed by polymerase chain reaction(PCR) with restriction fragment length polymorphism(RFLP) method. The multiple covariance analysis was used to compare olive trail moment and comet trail length adjusted confounding factors. RESULTS: In formaldehyde exposed workers, after ages, smoking and drinking status and occupational exposure level were adjusted, means of Olive trail moment and comet trail length in the subjects with variant genotype at Arg280 His site (geometric means 4.30 and 13.42 respectively) were higher than subjects with wild type homozygote (geometric means 3.38 and 11.71 respectively), the differences were significant (Olive trail moment: P < 0.05, comet trail length: P < 0.01) . No associations between the polymorphisms at other three sites in XRCC1 gene and means of olive trail moment and comet trail length in exposure workers were found. CONCLUSION: The polymorphisms of XRCC1 gene may modulate the effects of DNA damages induced by formaldehyde in workers.

[Early genetic effects on workers occupationally exposed to formaldehyde].

OBJECTIVE: To investigate the DNA and chromosome damage in peripheral blood lymphocyte of workers occupationally exposed to formaldehyde (FA). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

[Follow-up study on psychic and neuropathic delayed effects of acute organophosphorus pesticides poisoning].

OBJECTIVE: To study the delayed effect on neuropsychopathy and its related factors after acute organophosphorus pesticides poisoning (AOPP). METHODS: Two hundred and fifty-seven cases of AOPP in the observation period were chosen to follow-up 2 months later from the 4 county hospitals in Shandong Province where the incidence of organophosphorus pesticide poisoning is high. RESULTS: Nine cases of organophosphate induced delayed polyneuropathy (OPIDP) were found and the incidence rate was 3.5%. The occurrence of OPIDP were related to the need for emergent artificial respiration, and the degree of poisoning, and the kinds of organophosphorus pesticides (Ops). The positive rate of symptoms of peripheral nerves, central nerves and psychogeny except auditory and visual hallucination after poisoning was significantly higher than that before (P < 0.05). The patient's situation of health, economy and work became statistically worse (P < 0.05). CONCLUSION: We found some had delayed effects on neuropsychopathy after AOPP which could debase the patient's life quality. The control measure should be administered as early as possible.

[Effects of 2,5-hexanedione on NGF expression in motor and sensory neuronal cells of rats].

OBJECTIVE: To investigate the effects of 2,5-Hexanedione (2,5-HD), a metabolite of n-hexane,on nerve growth factor (NGF) expression in motor and sensory neuronal cells of peripheral nervous system of rats. METHODS: Primary cultured dorsal root ganglion (DRG) neurons were obtained from new born rats on day 4. The cell line VSC4.1 were cultured. The growth condition of cells were observed with a phase contrast microscope. Immunohistochemistry technology was used to analyze the NGF expression in both VSC4.1 cells and primary cultured DRG cells treated with 4 different dosages of 2, 5-HD (2.5, 5.0, 10.0, 20.0 mmol/L) respectively for 24 hours. RESULTS: The NGF expression decreased significantly in both DRG neurons and VSC4.1 cells dosed respectively with 5.0,10.0,20.0 mmol/L 2,5-HD in comparison with the control group (P < 0.05), with a tendency of dose-effect correlation. CONCLUSION: The results suggested that 2,5-HD can decrease the endogenous NGF levels in both cultured DRG sensory neurons and VSC4.1 motor neuron cells of rats.

[Association of XRCC1 polymorphisms and chromosomal damage levels in coke-oven workers].

OBJECTIVE: To investigate the association of XRCC1 polymorphisms and chromosomal damage levels in peripheral blood lymphocyte in coke-oven workers. METHODS: 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. RESULTS: 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. CONCLUSIONS: The genetic polymorphisms of XRCC1 gene could influence the chromosome damage levels in coke-oven workers.

[Association of metabolic and DNA repair enzyme gene polymorphisms and DNA damage in coke-oven workers].

OBJECTIVE: To investigate the association of polymorphisms of metabolic and DNA repair enzyme genes and DNA damage in peripheral blood lymphocytes in coke-oven workers. METHODS: 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. RESULTS: 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). CONCLUSION: XRCC1 and GSTP1 polymorphisms might influence the susceptibility of DNA damage in occupational PAH-exposed coke-oven workers.

The association of XRCC1 haplotypes and chromosomal damage levels in peripheral blood lymphocyte among coke-oven workers.

Theoretically, a haplotype has a higher level of heterozygosity than individual single nucleotide polymorphism (SNP) and the association study based on the haplotype may have an increased power for detecting disease associations compared with SNP-based analysis. In this study, we investigated the effects of four haplotype-tagging SNPs (htSNP) and the inferred haplotype pairs of the X-ray cross-complementing group 1 (XRCC1) gene on chromosome damage detected by the cytokinesis-block micronucleus assay. The study included 141 coke-oven workers with exposure to a high level of polycyclic aromatic hydrocarbons and 66 nonexposed controls. The frequencies of total MN and MNed cells were borderline associated with the Arg(194)Trp polymorphism (P = 0.053 and P = 0.050, respectively) but not associated with the Arg(280)His, Arg(399)Gln and Gln(632)Gln polymorphisms among coke-oven workers. Five haplotypes, including CGGG, TGGG, CAGG, CGAG, and CGGA, were inferred based on the four htSNPs of XRCC1 gene. The haplotype CGGG was associated with the decreased frequencies of total MN and MNed cells, and the haplotypes TGGG and CGAG were associated with the increased frequencies of total MN and MNed cells with adjustment for covariates among coke-oven workers. This study showed that the haplotypes derived from htSNPs in the XRCC1 gene were more likely than single SNPs to correlate with the polycyclic aromatic hydrocarbon-induced chromosome damage among coke-oven workers.

Functional changes of nicotinic acetylcholine receptor in muscle and lymphocyte of myasthenic rats following acute dimethoate poisoning.

The mechanism underlying intermediate myasthenia syndrome (IMS) following acute organophosphate poisoning remains largely unknown. Previous studies indicated that the mechanism of myasthenia in rats and IMS patients is most likely due to a postsynaptic neurotransmission blocking at neuromuscular junctions (NMJ). Nicotinic acetylcholine receptor (nAChR) is a key postsynaptic component at NMJ. Whether functional changes of nAChR are related to the development of myasthenia has not been demonstrated and addressed in vivo so far. In this study, we attempted to investigate temporal and spatial changes of nAChR in the blood lymphocyte, muscle and brain of rats during the course of myasthenia after acute dimethoate poisoning by using radioligand-binding assay. We found that specific nAChR binding activity in the gastrocnemius muscle and blood lymphocytes of myasthenia rats was significantly increased at 48h after dimethoate poisoning. However, no changes of nAChR binding activity were found in the lymphocytes and muscle of non-myasthenia rats which were sacrificed at 1h after intoxication. Interestingly, no changes of nAChR and muscarinic acetylcholine receptor (mAChR) binding activity were found in the cerebrum and cerebellum of all rats after dimethoate intoxication either at 1 or 48h. The change of nAChR specific binding activity in the lymphocytes is parallel with that in the skeletal muscle during the development of myasthenia. This implied that the changes of nAChR receptor binding activity in the skeletal muscle and lymphocytes are highly associated with the development of myasthenia. The functional changes of nAChR at NMJ might play an important role in the paralysis of skeletal muscle following acute organophosphates (OPs) poisoning.

Effects of genetic polymorphisms of metabolic enzymes on cytokinesis-block micronucleus in peripheral blood lymphocyte among coke-oven workers.

Exploring the associations between genetic polymorphisms of metabolic enzymes and susceptibility to polycyclic aromatic hydrocarbon (PAH)-induced chromosomal damage is of great significance for understanding PAH carcinogenesis. Cytochrome P450, glutathione S-transferase, microsomal epoxide hydrolase, NAD(P)H:quinone oxidoreductase, and N-acetyltransferase are PAH-metabolizing enzymes. In this study, we genotyped for the polymorphisms of these genes and assessed their effects on cytokinesis-block micronucleus (CBMN) frequencies in peripheral blood lymphocytes among 141 coke-oven workers and 66 non-coke-oven worker controls. The geometric means of urinary 1-hydroxypyrene levels in coke-oven workers and the controls were 12.0 and 0.7 micromol/mol creatinine, respectively (P < 0.01). The CBMN frequency (number of micronuclei per 1,000 binucleated lymphocytes) was significantly higher in coke-oven workers (9.5 +/- 6.6 per thousand) than in the controls (4.0 +/- 3.6 per thousand; P < 0.01). Among the coke-oven workers, age was positively associated with CBMN frequency; the mEH His113 variant genotype exhibited significantly lower CBMN frequency (8.5 +/- 6.5 per thousand) than did the Tyr113/Tyr113 genotype (11.3 +/- 6.4 per thousand; P < 0.01); the low mEH activity phenotype exhibited a lower CBMN frequency (8.6 +/- 6.8 per thousand) than did the high mEH activity phenotype (13.2 +/- 6.7 per thousand; P = 0.01); the GSTP1 Val105/Val105 genotype exhibited a higher CBMN frequency (15.0 +/- 5.8 per thousand) than did the GSTP1 Ile105/Ile105 or Ile105/Val105 genotypes (9.3 +/- 6.5 per thousand; P < 0.01); the joint effect of high mEH activity phenotype and GSTM1 null genotype on CBMN frequencies was also found. Gene-environment interactions between occupational PAH exposure and polymorphisms of mEH and/or GSTM1 were also evident. These results indicate that the mEH, GSTP1, and GSTM1 polymorphisms may play a role in sensitivity or genetic susceptibility to the genotoxic effects of PAH exposure in the coke-oven workers.

[Effect of genetic polymorphisms of microsomal epoxide hydrolase on urinary 1-hydroxypyrene levels in coke oven workers].

OBJECTIVE: To investigate the associations of polymorphisms of metabolic enzyme genes with urinary 1-hydroxypyrene levels in coke oven workers. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

[Relationship of polycyclic aromatic hydrocarbon exposure with peripheral blood lymphocyte DNA damage in coke oven workers].

OBJECTIVE: To investigate the relationship between lymphocyte DNA damage and polycyclic aromatic hydrocarbons (PAHs) exposure in coke oven workers. METHODS: 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. RESULTS: 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. CONCLUSION: There are dose-effect and dose-response relationships between PAHs exposure and lymphocyte DNA damage in coke oven workers.

[A study on the inherited susceptibility of chromosomal damage in peripheral blood lymphocytes among coke oven workers].

OBJECTIVE: To investigate the association between polymorphisms of metabolic enzyme genes and chromosomal damage risk in peripheral blood lymphocytes among coke oven workers. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

[Genetic damage in peripheral blood lymphocyte of coke oven workers].

OBJECTIVE: To investigate DNA and chromosome damage in peripheral blood lymphocyte of coke oven workers exposed to polycyclic aromatic hydrocarbons (PAHs). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Associations between XRCC1 and ERCC2 polymorphisms and DNA damage in peripheral blood lymphocyte among coke oven workers.

A wide variety of base damages and single-strand breaks formed by reactive oxygen species during metabolic activation of polycyclic aromatic hydrocarbons (PAHs) have been recognized to be involved in PAH carcinogenesis. In this study, alkaline comet assay was used to detect the DNA damage in peripheral blood lymphocytes among 143 coke-oven workers and 50 non-coke-oven workers, and the effects of genetic polymorphisms of XRCC1 and ERCC2 genes on DNA damage were evaluated. The olive tail moment was significantly higher in coke-oven workers than in non-coke-oven workers (2.6, 95% CI=2.1-3.3 versus 1.0, 95% CI=0.8-1.2, p<0.01), and significant correlation between ln-transformed urinary 1-OHP and ln-transformed olive tail moment was found in total population (n=193, Pearson's r=0.393, p<0.001) and in coke-oven workers (n=143, Pearson's r=0.224, p=0.007). The olive tail moment was significantly higher in coke-oven workers with GA genotype of G27466A polymorphism of XRCC1 than those with GG genotype (4.6, 95% CI=2.5-8.7 versus 2.4, 95% CI=1.9-2.9, p<0.01 with adjustment for covariates). No significant associations between C26304T, G28152A and G36189A polymorphisms of XRCC1 and G23591A and A35931C polymorphisms of ERCC2 and olive tail moment were found in both groups. The study showed that the alkaline comet assay is a suitable biomarker in the detection of DNA damage among coke-oven workers and it suggested that the A allele of G27466A polymorphism of XRCC1 may be associated with decreased DNA repair capacity toward PAH-induced base damage and strand breaks.

Genes differentially expressed in human lung fibroblast cells transformed by glycidyl methacrylate.

OBJECTIVE: To define the differences in gene expression patterns between glycidyl methacrylate (GMA)-transformed human lung fibroblast cells (2BS cells) and controls. METHODS: The mRNA differential display polymerase chain reaction (DD-PCR) technique was used. cDNAs were synthesized by reverse transcription and amplified by PCR using 30 primer combinations. After being screened by dot blot analysis, differentially expressed cDNAs were cloned, sequenced and confirmed by Northern blot analysis. RESULTS: Eighteen differentially expressed cDNAs were cloned and sequenced, of which 17 were highly homologous to known genes (homology = 89%-100%) and one was an unknown gene. Northern blot analysis confirmed that eight genes encoding human zinc finger protein 217 (ZNF217), mixed-lineage kinase 3 (MLK-3), ribosomal protein (RP) L15, RPL41, RPS 16, TBX3, stanniocalcin 2 (STC2) and mouse ubiquitin conjugating enzyme (UBC), respectively, were up-regulated, and three genes including human transforming growth factor beta inducible gene (Betaig-h3), alpha-1,2-mannosidase 1A2 (MAN 1A2) gene and an unknown gene were down-regulated in the GMA-transformed cells. CONCLUSION: Analysis of the potential function of these genes suggest that they may be possibly linked to a variety of cellular processes such as transcription, signal transduction, protein synthesis and growth, and that their differential expression could contribute to the GMA-induced neoplastic transformation.