Gene-specific promoter methylation is associated with micronuclei frequency in urothelial cells from individuals exposed to organic solvents and paints

Sufficient epidemiologic evidence has established an etiologic link between bladder cancer risk and occupational exposure as a painter to organic solvents. Currently, it remains to be established whether gene-specific promoter methylation contributes to bladder cancer development, including by enhancing chromosome breakage or loss. We investigated the effect of chronic exposure to organic solvents and paints on DNA methylation profiles in the promoter regions of four genes (GSTP1, p16 INK4a, APC and CDH1) and micronucleus (MN) frequency in exfoliated urothelial cells from voided urine from Colombian male non-smoking car painters and age-matched unexposed individuals. The exposed group had a higher percentage of individuals with >2 MNs/2000 cells compared with the unexposed group (P=0.04). Gene-specific analysis showed a significantly higher percentage of individuals with methylated GSTP1, p16 INK4a and APC in the exposed group. Poisson regression analysis indicated that exposed individuals with methylated GSTP1 and p16 INK4a promoters were more than twofold more likely to have an increase in MN frequency as compared with the reference. Finally, among exposed individuals with GSTP1 and p16 INK4a methylated promoters, those with a greater age had a higher RR of increased MN frequency compared with younger exposed individuals with methylated promoters. These results support the conclusion that gene-specific promoter methylation may increase MN frequency in a dependent or independent interaction with occupational exposure to organic solvents.