Micronucleus frequency in buccal cells increases with urinary titanium concentrations and oxidative stress biomarkers among subway workers

The micronucleus (MN) assay in buccal cells is a widely used, non-invasive biomarker for detecting genotoxic effects in human populations. However, its application in assessing dose-response relationships to particulate matter exposure remains limited. Our aim was to evaluate the association between MN frequency in exfoliated buccal cells and exposure to subway particulate matter among Parisian subway workers. We also investigated whether MN frequency was associated with biomarkers of oxidative stress and metabolism-related effects. We recruited 303 subway workers and collected their buccal cell samples. Concentrations of metals in urine and exhaled breath condensate were quantified using inductively coupled plasma mass spectrometry, and effect biomarkers were analyzed via liquid chromatography-mass spectrometry. Factor analyses were used to characterize metal mixtures and oxidative stress profiles. Associations with MN frequency were assessed using multivariable Poisson regression models adjusted for confounders. Despite that all 269 workers who provided buccal cell samples had low exposures, urinary titanium concentrations were significantly associated with increased MN frequency (RR = 2.013, p = 0.004). Furthermore, oxidative stress constituting mainly of urinary malondialdehyde and 8-hydroxy-2'-deoxyguanosine showed a statistically significant association with increased MN frequency in buccal cells (RR = 1.214, p = 0.045). Women exhibited a significantly lower MN frequency in buccal cells compared to men. No statistically significant associations were found with PM₁₀ air concentrations nor employment duration. Urinary titanium concentrations and oxidative stress biomarkers were significantly associated with MN frequency in buccal cells, suggesting that MN frequency may reflect systemic biological effects even in low-exposure settings.