Oxidative stress and lipid peroxidation quantified with M1dG in nasal epithelia workers exposed to formaldehyde

Abstract

Formaldehyde (FA) is a ubiquitous chemical widely used for various industrial purposes. FA was recently reclassified by the IARC as a human carcinogen, based on sufficient evidence for a casual role for nasopharyngeal cancer. We conducted a cross-sectional study aimed to compare the frequency of M1dG adducts, a biomarker of oxidative stress and lipid peroxidation, in the nasal epithelia of 50 plastic laminate plant workers FA-exposed in respect to 45 controls by 32P-DNA postlabeling. The personal levels of FA exposure were analysed by HPLC. Smoking status was estimated by measuring urinary cotinine by gaschromatography mass-spectrometry. Air monitoring results showed that the levels of FA were significantly increased in the plastic laminate plant, 211.4 ± 14.8 (SE) µg/m3, as compared to controls, 35.2 ± 3.4 (SE) µg/m3, p < 0.001. The levels of urinary cotinine were 1064 ± 118 ng/ml and 14.18 ± 2.5 ng/ml in smokers and non-smokers, respectively, p < 0.001. M1dG adduct frequency per 108 normal nucleotides was significantly higher within the workers exposed to FA, 111.6 ± 14.3 (SE), as compared to controls, 49.6 ± 3.4 (SE), p < 0.001. After subgrouping for exposure levels, M1dG was significantly increased in the subjects exposed to more than 66 µg/m3 of FA. No influences of smoking and age were observed in all the study population. However, after categorizing for occupational exposure, a significant effect was found in the controls, p = 0.018, where the levels of DNA damage were significantly correlated with the levels of cotinine, regression coefficient (β) = 0.494 ± 0.000 (SE), p < 0.002. Our findings indicated that the generation of M1dG adducts can constitute a potential mechanism of FA-induced toxicity. Persistent DNA damage can contribute to the general decline of the physiological mechanisms designed to maintain cellular homeostasis, up to cell death, senescence, uncontrolled proliferation and genome instability.