Objective To study possible mechanisms of oxidative damages in rat lung type Ⅱ cells induced by cooking oil fume (COF). Methods The rat type Ⅱ lung cells were pretreated with anti_oxidant N_acetylcysteine (NAC) for 30 miuntes and were exposed to COF for 12 hours. The contents of MDA and GSH were detected with thiobarbituric acid colorimetric assay and 5,5_dithiobis 2_nitrobenzoic acid colorimetric assay. Results The significant increase of the contents of MDA and significant decrease of the contents of GSH were observed in the rat lung type Ⅱ cells with the increase of exposure doses of COF and the prolongation of exposure time of COF. The pretratment of NAC could reduce the production of MDA and increase the contents of GSH of the cells. Conclusion The possible mechanisms of oxidative damages in rat lung type Ⅱ cells induced by cooking oil rume might be formation of lipid peroxidation and interference of GSH anti_oxidative systems of the cells.

Objective To investigate the genetic damage of human bronchial epithelial cells (HBE) caused by cigarette smoke combined with nano-TiO2.Methods 16-HBE cells were exposed to cigarette smoke extract (CSE) and nano-TiO2(mg/L) at the doses of 0 mg/L CSE+0 mg/L nano-TiO2,50 mg/L CSE+0 mg/L nano-TiO2,75 mg/L CSE+0 mg/L nano-TiO2,100 mg/L CSE+0 mg/L nano-TiO2,0 mg/L CSE+10 mg/L nano-TiO2,50 mg/L CSE+10 mg/L nano-TiO2,75 mg/L CSE+10 mg/L nano-TiO2,100 mg/L CSE+10 mg/L nano-TiO2. After 24 h exposure,HBE viability was evaluated by the methyl thiazolyl tetrazolium (MTT) assay,single cell gel electrophoresis (SCGE,comet assay) was employed to assess DNA damage,chromosomal aberration was measured by micronucleus test. Results Except the group exposed to 10 mg/L nano-TiO2,HBE viability of the other treatment groups were lower than that of the control group and Comet % of the other treatment groups were higher than that of the control group (P

OBJECTIVECytochrome P450 2E1 (CYP2E1) is an important metabolizing enzyme involved in oxidative stress responses to benzene, a chemical associated with bone marrow toxicity and leukemia. We aimed to identify the CYP2E1 genetic biomarkers of susceptibility to benzene toxicity in support of environmental and occupational exposure prevention, and to test whether a model using immortal human lymphocytes might be an efficient tool for detecting genetic biomarkers.

METHODSImmortalized human lymphocyte cell lines with independent genotypes on four CYP2E1 SNP sites were induced with 0.01% phenol, a metabolite of benzene. CYP2E1 gene function was evaluated by mRNA expression and enzyme activity. DNA damage was measured by Single-Cell Gel Electrophoresis (SCGE).

RESULTSAmong the four SNPs, cells with rs2070673TT and rs2030920CC showed higher levels of CYP2E1 transcription and enzymatic activity than the other genotypes in the same SNP site. Cells with higher gene expression genotypes also showed higher comet rates compared with lower gene expression genotypes.

CONCLUSIONThese results suggest that CYP2E1 rs2070673 and rs2030920 might be the genetic biomarkers of susceptibility to benzene toxicity and that the immortalized human lymphocytes model might be an efficient tool for the detection of genetic biomarkers of susceptibility to chemicals.

Adolescent ; Adult ; Asian Continental Ancestry Group ; Benzene ; metabolism ; pharmacology ; Cell Line ; Cell Proliferation ; drug effects ; Cytochrome P-450 CYP2E1 ; genetics ; Humans ; Lymphocytes ; drug effects ; metabolism ; Middle Aged ; Phenol ; metabolism ; pharmacology ; Young Adult

Objective To investigate the association between single nucleotide polymorphisms(SNPs)of YTHDF1 rs6011668,HNRNPA2B1 rs2070601 and rs76558212 with the risk of gastric cancer.Methods A total of 457 cases with gastric cancer and 525 healthy controls were collected.The candidate SNPs were genotyped using Hi-SNP genotyping methods by multiplex rounds of PCR and high-throughput sequencing;the association between the three SNPs with the risk of gastric cancer was analyzed by test and Logistic regression.Multifactorial logistic regression and Risk Score(RS)model was used to analyze the influence of environmental and genetic factors on the risk of gastric cancer.Results YTHDF1rs6011668 TT genotype carriers had 3.075 times higher risk of gastric cancer than CC genotype carriers(95%CI:1.128～8.382,P = 0.028),and 2.961 times higher risk than CC/TC genotypes carriers(95%CI:1.091～8.033,P = 0.033).Subgroups-analysis revealed that TT genotype mainly increased the risk of gastric cancer in non-tea drinkers,pickled food eaters and fried food eaters(P<0.05).In addition,TT genotype carriers had the increased risk of gastric cancer infiltration,lymph node metastasis,distal metastasis and intermediate to advanced stages(P<0.05).The RS of the case and control groups were calculated by combining environmental and genetic factors.The higher the RS score,the higher the risk of gastric cancer was found in the RS quartile groups.Compared with the RS

Background N6-methyladenosine (m6A) RNA methylation may play an important role in the process of malignant transformation of cells induced by environmental carcinogens. However, the specific roles and mechanisms need to be further explored. Objective To explore the role and mechanism of m6A binding protein insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) in the malignant transformation of human gastric mucosal epithelial cells GES-1 induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Methods Based on the GES-1 malignant transformation cells MC-30, a stable knockdown IGF2BP3 MC-30 cell line (MC30-shIGF2BP3, abbreviated as MC30-shI3) was constructed by lentiviral transfection technology, and a negative control group (MC30-NC) was also prepared. Real-time quantitative polymerase chain reaction (qRT-PCR) and Western blotting were applied to detect the mRNA expression and protein levels of IGF2BP3. RNA binding protein immunoprecipitation (RIP-qPCR) was used to examine the combination between IGF2BP3 protein and MYC mRNA in malignant cells MC-30. Furthermore, the stability of MYC mRNA was detected by actinomycin D assay. CCK-8 and Transwell respectively were employed to detect cell proliferation, migration, and invasion. Western blotting was applied to detect the expression of EMT markers (N-cadherin, Vimentin, α-SMA, and Snail). The role of the downstream target gene MYC was further elucidated by a rescue assay in MC30-shI3 cells transfected with a plasmid overexpressing MYC to observe changes in cellular phenotypes (proliferation, migration, invasion) and expression of key EMT proteins. Results Compared with the control group, the expression of IGF2BP3 mRNA was up-regulated after 5, 10, 20, and 40 μmol·L⁻¹ MNNG infection of GES-1 cells (P<0.05). After 20 μmol·L⁻¹ MNNG infection, the expression level of IGF2BP3 mRNA increased with prolongation of exposure time (P<0.05). Compared with the control group, the mRNA and protein expression levels of IGF2BP3 were up-regulated in the 10th, 20th, and 30th generations of 5 μmol·L⁻¹ MNNG malignant transformation (P<0.05). The results of qRT-PCR and Western blotting showed that, compared with the MC30-NC group, the IGF2BP3 and MYC mRNA expression and protein expression decreased in the MC30-shI3 group (P<0.01). The CCK8 and transwell assay results showed that, compared with the MC30-NC group, the cell proliferation, migration, and invasion abilities significantly reduced in the MC30-shI3 group (P<0.01). The results of the Western blotting showed that, compared with the MC30-NC group, the protein levels of EMT markers N-cadherin, Vimentin, α-SMA, and Snail decreased in the MC30-shI3 group (P<0.01). The results of RIP-qPCR showed that, compared with the IgG group, the mRNA level was higher for the enriched MYC in the IGF2BP3 group (P<0.01); the results of the actinomycin D assay showed that, compared with the MC30-NC group, the stability of MYC mRNA significantly reduced in the MC30-shI3 group (P<0.01). While the rescue experiment showed that, compared with the IGF2BP3 knock-down+vector group, the MYC protein level significantly increased in the IGF2BP3 knock-down + MYC over-expression group (P<0.01), the proliferation, migration, and invasion abilities significantly enhanced (P<0.01), and the EMT key proteins (N-cadherin, Vimentin, α-SMA, Snail) increased in the MC30-shI3+MYC group (P<0.01). Conclusion Exposure to MNNG could result in up-regulation of IGF2BP3 expression in GES-1 cells. IGF2BP3 may enhance the proliferation, migration, and invasion of malignantly transformed human gastric epithelial cells by binding to MYC mRNA and increasing its stability and expression level and thus promoting the EMT process, which in turn affects the progression of malignant transformation.

Background Cumulative fatigue without intervention will seriously threaten the physical and mental health of workers. Shift work and life satisfaction are strongly associated with fatigue accumulation. Objective To explore the effects of life satisfaction, shift work, and their interaction on cumulative fatigue in petrochemical employees, and to provide a scientific basis for preventing cumulative fatigue. Methods All staff of a petrochemical enterprise were selected by cluster sampling for a cross-sectional study from July to October 2021 in Jiangsu Province. A questionnaire designed by the project team was used to collect information on shift work; and life satisfaction and cumulative fatigue were investigated by the World Health Organization Five-item Well-Being Index and the Self-diagnosis Checklist for Assessment of Worker’s Fatigue Accumulation respectively. A logistic regression model was used to analyze the influences of life satisfaction and shift work on cumulative fatigue. Multiplicative and additive models were applied to analyze the interaction effect of life satisfaction and shift work. Results A total of 4066 questionnaires were returned, of which 3763 were valid, with an effective recovery rate of 92.5%. The percentage of cumulative fatigue in the petrochemical employees was 63.2% (2377/3763), and the percentages of low life satisfaction and shift work in the petrochemical employees were 53.6% (2016/3763) and 54.2% (2041/3763), respectively. The results of univariate analysis showed no significant difference in cumulative fatigue among different marital status groups (P=0.176), and there were statistically significant differences in cumulative fatigue among the petrochemical employees in different groups of age, gender, educational level, average monthly income, job title, length of service, working hours, night shift, smoking, drinking, physical exercise, life satisfaction, and shift work (P<0.001). After adjustment for covariates such as age, gender, educational level, average monthly income, job title, length of service, working hours, night shift, smoking, drinking, and physical activity, the unconditional logistic regression model showed that the risk of reporting cumulative fatigue in high life satisfaction participants was 0.129 (95%CI: 0.109, 0.154) times of that in participants of low life satisfaction; the risk of reporting cumulative fatigue in shift work participants was 3.792 (95%CI: 2.713, 5.300) times of that in no shift work participants; and the risk of reporting cumulative fatigue in participants with both high life satisfaction and shift work was 0.105 (95%CI: 0.081, 0.135) times of that in participants with low life satisfaction and shift work. The relative excess risk due to interaction, the attributable proportion due to interaction, and the synergy index of coexisting life satisfaction and shift work were −5.504 (95%CI: −7.247, −3.760), −4.728 (95%CI: −7.575, −1.880), and 0.029 (95%CI: 0.002, 0.351) respectively, which suggested that life satisfaction and shift work have an additive interaction effect on cumulative fatigue. A significant multiplicative interaction was also found between life satisfaction and shift work (OR=0.688, 95%CI: 0.476, 0.936). Conclusion Life satisfaction and shift work are the influencing factors of cumulative fatigue among petrochemical employees, and they interact with each other on the risk of cumulative fatigue. High life satisfaction can reduce the risk of accumulated fatigue associated with shift work.