Abstract: Objective To investigate the effects of VEGF,HIF-1 and TRX mRNA expression change s induced by nickel on human lungfibroblasts(WI-38)in the process of malignant transformation.Methods WI-38 cells were treated with Ni₂O₃ for 24h,48h and 72h.The expression changes of thioredoxin(TRX),hypoxia-inducible transcr iption factor-1(HIF-1)and vascular endo the lial growth factor(VEGF)gene were tested by RT-PCR.Results The VEGF mRNA expressions(log cDNA/log-actin)in WI-38 cells treated with different concen trations of Ni₂O₃(5μg/ml.10μg/ml and 15μg/ml)for 24 hours(0.76±0.04,0.78±0.06 and 0.69±0.01,respectively)were higher than that of in control g roup(0.58±0.02,P<0.05).The over-expressions of VEGF were also found in 48h-Ni₂O₃ treated and 72h-Ni₂O₃ treated groups.The TRX expressions were down-regulated in WI-38 cells trea ted with different concentrations of Ni₂O₃ for 72 hours compared with the control cells(0.36±0.15,0.31±0.07 and 0.31±0.02 vs 1.06±0.09,P<0.05).The HIF-1 expressions of 5μg/ml and 10μg/ml Ni₂O₃ group cells were increased at 48 hours(1.01±0.04 and 0.82±0.12) and decreased after 72 hours(0.66±0.10 and 0.69±0.13)compared with control cells(0.47±0.02,P<0.05).However 15μg/ml nickel groups(24h,48h and 72h)were no significant difference compared with control group.Conclusion The expression changes in genes a ssociated with oxidative stress such as VEGF,HIF-1 and TRX induced by nicke lmiplicated that nickel-mediated oxidative processe smay partic ipate in the molecular pathways of malignant transformation and carcinogenicity.