Objectives The role of iron on Reactive Oxygen Species (ROS) generation by catalysing Fenton reaction have been suggested by many studies as an important factor in increasing oxidative DNA damage. Mitochondria represents an important biological source and target of ROS that induce 8-hydroxy-2̀’-deoxyguanosine (8-OHdG) formation. Occupational exposure to metal rich air particles, as reported in steel production process, constitutes an important source of metal exposure, in particular to iron.
Methods We measured 8-OHdG in mitochondrial DNA (mtDNA), by real-time PCR, in blood leukocytes from 113 healthy male foundry workers (mean age = 42.2 years, SD = 11.2) with high levels of exposure to metal-rich particles. Exposure to iron and others metals, was assessed in urine collected the same day of blood sampling, at the end of the standard working week. Multivariable regression models adjusted for age, body mass index (BMI), and smoking were designed to evaluate the relationship between urinary markers of exposure and 8-OHdG in mtDNA To assure normal distribution, 8-OHdG in mtDNA data were loge transformed, and the regression slopes were exponentiated to obtain the geometric mean ratio (GMR) for increments in one SD of exposure.
Results After a week of exposure, elevated levels of urinary iron, (mean Fe = 10.9 µg/g creat, SD = 7.9) were found among enrolled workers. Individual exposure level resulted positively associated with 8-OHdG formation in mtDNA in peripheral blood leukocytes (GMR = 1.22 p = 0.03). The observed association was confirmed also after adjustment for potential confounders: age, BMI, and smoking (GMR = 1.22; p = 0.04).
Conclusions Our observation of exposure-related high levels of 8-HOdG suggests that iron exposure may induce mtDNA damage, a potential response to oxidative stress caused by iron-induced production of ROS. The potential toxicity of high-level of iron exposure due to 8-HOdG generation and its ability to induce G-T base modification deserves further investigation.
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