title: Gene-specific promoter methylation is associated with micronuclei frequency in urothelial cells from individuals exposed to organic solvents and paints.
abstract: 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.
authors.affiliation: Department of Biology, Research Group Genetic Toxicology and Cytogenetics, Faculty of Natural Sciences and Education, Universidad del Cauca, Popayán, Cauca, Colombia.
authors.forename: L S
authors.initials: LS
authors.lastname: Hoyos-Giraldo
authors.affiliation: Department of Biology, Research Group Genetic Toxicology and Cytogenetics, Faculty of Natural Sciences and Education, Universidad del Cauca, Popayán, Cauca, Colombia.|Departments of Pharmacological Sciences and Pathology, Stony Brook University, Stony Brook, New York, USA.
authors.forename: L F
authors.initials: LF
authors.lastname: Escobar-Hoyos
authors.affiliation: Department of Biology, Research Group Genetic Toxicology and Cytogenetics, Faculty of Natural Sciences and Education, Universidad del Cauca, Popayán, Cauca, Colombia.
authors.forename: D
authors.initials: D
authors.lastname: Saavedra-Trujillo
authors.affiliation: Department of Biology, Research Group Genetic Toxicology and Cytogenetics, Faculty of Natural Sciences and Education, Universidad del Cauca, Popayán, Cauca, Colombia.
authors.forename: I
authors.initials: I
authors.lastname: Reyes-Carvajal
authors.affiliation: Department of Biology, Research Group Genetic Toxicology and Cytogenetics, Faculty of Natural Sciences and Education, Universidad del Cauca, Popayán, Cauca, Colombia.
authors.forename: A
authors.initials: A
authors.lastname: Muñoz
authors.affiliation: Department of Biology, Research Group Genetic Toxicology and Cytogenetics, Faculty of Natural Sciences and Education, Universidad del Cauca, Popayán, Cauca, Colombia.
authors.forename: E
authors.initials: E
authors.lastname: Londoño-Velasco
authors.affiliation: Department of Biology, Research Group Genetic Toxicology and Cytogenetics, Faculty of Natural Sciences and Education, Universidad del Cauca, Popayán, Cauca, Colombia.
authors.forename: A
authors.initials: A
authors.lastname: Tello
authors.affiliation: Department of Biology, Research Group Genetic Toxicology and Cytogenetics, Faculty of Natural Sciences and Education, Universidad del Cauca, Popayán, Cauca, Colombia.
authors.forename: N
authors.initials: N
authors.lastname: Cajas-Salazar
authors.affiliation: Department of Morphology, Research Group Health and Work, Faculty of Health Sciences, Universidad del Cauca, Popayán, Cauca, Colombia.
authors.forename: M
authors.initials: M
authors.lastname: Ruíz
authors.affiliation: Department of Biology, Research Group Genetic Toxicology and Cytogenetics, Faculty of Natural Sciences and Education, Universidad del Cauca, Popayán, Cauca, Colombia.
authors.forename: S
authors.initials: S
authors.lastname: Carvajal
authors.affiliation: Department of Environmental Health Sciences, Mailman School of Public Health of Columbia University, New York, New York, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Santella
mesh_terms: D019175:DNA Methylation; D006801:Humans; D008297:Male; D015162:Micronucleus Tests; D016273:Occupational Exposure; D010150:Paint / Q000633:toxicity*; D011401:Promoter Regions, Genetic; D012997:Solvents / Q000633:toxicity*; D019459:Urothelium / Q000166:cytology / Q000187:drug effects*
chemical_list: D012997:Solvents