title: Polymorphisms in metabolism and repair genes affects DNA damage caused by open-cast coal mining exposure.
abstract: Increasing evidence suggest that occupational exposure to open-cast coal mining residues like dust particles, heavy metals and Polycyclic Aromatic Hydrocarbons (PAHs) may cause a wide range of DNA damage and genomic instability that could be associated to initial steps in cancer development and other work-related diseases. The aim of our study was to evaluate if key polymorphisms in metabolism genes CYP1A1Msp1, GSTM1Null, GSTT1Null and DNA repair genes XRCC1Arg194Trp and hOGG1Ser326Cys could modify individual susceptibility to adverse coal exposure effects, considering the DNA damage (Comet assay) and micronucleus formation in lymphocytes (CBMN) and buccal mucosa cells (BMNCyt) as endpoints for genotoxicity. The study population is comprised of 200 healthy male subjects, 100 open-cast coal-mining workers from "El Cerrejón" (world's largest open-cast coal mine located in Guajira - Colombia) and 100 non-exposed referents from general population. The data revealed a significant increase of CBMN frequency in peripheral lymphocytes of occupationally exposed workers carrying the wild-type variant of GSTT1 (+) gene. Exposed subjects carrying GSTT1null polymorphism showed a lower micronucleus frequency compared with their positive counterparts (FR: 0.83; P=0.04), while BMNCyt, frequency and Comet assay parameters in lymphocytes: Damage Index (DI) and percentage of DNA in the tail (Tail % DNA) were significantly higher in exposed workers with the GSTM1Null polymorphism. Other exfoliated buccal mucosa abnormalities related to cell death (Karyorrhexis and Karyolysis) were increased in GSTT/M1Null carriers. Nuclear buds were significantly higher in workers carrying the CYP1A1Msp1 (m1/m2, m2/m2) allele. Moreover, BMNCyt frequency and Comet assay parameters were significantly lower in exposed carriers of XRCC1Arg194Trp (Arg/Trp, Trp/Trp) and hOGG1Ser326Cys (Ser/Cys, Cys/Cys), thereby providing new data to the increasing evidence about the protective role of these polymorphisms. This modulation may involve specific and differentiated pathways in different tissues that also may cause a differential sensitivity related to differential induction of some enzymes.
authors.affiliation: Programa de Pós Graduação em Biologia Celular e Molecular (PPGBCM), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil; Departamento de Biofísica, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil; Laboratorio de Investigación Biomédica y Biología Molecular, Universidad del Sinú, Montería, Córdoba, Colombia. Electronic address: espitiaperez00@gmail.com.
authors.forename: Lyda
authors.initials: L
authors.lastname: Espitia-Pérez
authors.affiliation: Laboratorio de Investigación Biomédica y Biología Molecular, Universidad del Sinú, Montería, Córdoba, Colombia.
authors.forename: Milton Quintana
authors.initials: MQ
authors.lastname: Sosa
authors.affiliation: Laboratorio de Investigación Biomédica y Biología Molecular, Universidad del Sinú, Montería, Córdoba, Colombia.
authors.forename: Shirley
authors.initials: S
authors.lastname: Salcedo-Arteaga
authors.affiliation: Programa de Pós Graduação em Biologia Celular e Molecular (PPGBCM), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil; Departamento de Biofísica, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Grethel
authors.initials: G
authors.lastname: León-Mejía
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: Luz Stella
authors.initials: LS
authors.lastname: Hoyos-Giraldo
authors.affiliation: Instituto de Matemática e Estatística, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Hugo
authors.initials: H
authors.lastname: Brango
authors.affiliation: Programa de Pós-Graduação em Genética e Biologia Molecular (PPGGBM), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
authors.forename: Katia
authors.initials: K
authors.lastname: Kvitko
authors.affiliation: Laboratório de Genética Toxicológica, Universidade Luterana do Brasil, ULBRA, Canoas, RS, Brazil.
authors.forename: Juliana
authors.initials: J
authors.lastname: da Silva
authors.affiliation: Programa de Pós Graduação em Biologia Celular e Molecular (PPGBCM), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil; Departamento de Biofísica, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. Electronic address: pegas@cbiot.ufrgs.br.
authors.forename: João A P
authors.initials: JA
authors.lastname: Henriques
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003032:Coal Mining / Q000379:methods*; D003105:Colombia; D003430:Cross-Sectional Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D004249:DNA Damage; D045647:DNA Glycosylases / Q000235:genetics; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D056726:Genetic Association Studies; D005982:Glutathione Transferase / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008658:Inactivation, Metabolic / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure / Q000009:adverse effects*; D020641:Polymorphism, Single Nucleotide; D000076105:X-ray Repair Cross Complementing Protein 1; D055815:Young Adult
chemical_list: D019363:Cytochrome P-450 CYP1A1; D045647:DNA Glycosylases; D004268:DNA-Binding Proteins; D005982:Glutathione Transferase; D000076105:X-ray Repair Cross Complementing Protein 1; C569463:CYP1A1 protein, human; C413545:glutathione S-transferase T1; C479058:oxoguanine glycosylase 1, human
keywords: BMNCyt; CBMN; Comet assay; Genetic polymorphism; Open-cast coal mining