The influence of genetic polymorphisms in XRCC3 and ADH5 genes on the frequency of genotoxicity biomarkers in workers exposed to formaldehyde.
The International Agency for Research on Cancer classified formaldehyde as carcinogenic to humans because there is "sufficient epidemiological evidence that it causes nasopharyngeal cancer in humans". Genes involved in DNA repair and maintenance of genome integrity are critically involved in protecting against mutations that lead to cancer and/or inherited genetic disease. Association studies have recently provided evidence for a link between DNA repair polymorphisms and micronucleus (MN) induction. We used the cytokinesis-block micronucleus (CBMN assay) in peripheral lymphocytes and MN test in buccal cells to investigate the effects of XRCC3 Thr241Met, ADH5 Val309Ile, and Asp353Glu polymorphisms on the frequency of genotoxicity biomarkers in individuals occupationally exposed to formaldehyde (n = 54) and unexposed workers (n = 82). XRCC3 participates in DNA double-strand break/recombination repair, while ADH5 is an important component of cellular metabolism for the elimination of formaldehyde. Exposed workers had significantly higher frequencies (P < 0.01) than controls for all genotoxicity biomarkers evaluated in this study. Moreover, there were significant associations between XRCC3 genotypes and nuclear buds, namely XRCC3 Met/Met (OR = 3.975, CI 1.053-14.998, P = 0.042) and XRCC3 Thr/Met (OR = 5.632, CI 1.673-18.961, P = 0.005) in comparison with XRCC3 Thr/Thr. ADH5 polymorphisms did not show significant effects. This study highlights the importance of integrating genotoxicity biomarkers and genetic polymorphisms in human biomonitoring studies.
Escola Superior de Tecnologia da Saúde de Lisboa - Instituto Politécnico de Lisboa, Portugal. carina.ladeira@estesl.ipl.pt
Carina
C
Ladeira
Susana
S
Viegas
Elisabete
E
Carolino
Manuel C
MC
Gomes
Miguel
M
Brito
D000328:Adult; D000445:Aldehyde Oxidoreductases / Q000235:genetics*; D015415:Biomarkers / Q000032:analysis; D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D004784:Environmental Monitoring; D005260:Female; D005557:Formaldehyde / Q000633:toxicity*; D005787:Gene Frequency; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism; D008297:Male; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced / Q000706:statistics & numerical data; D015162:Micronucleus Tests; D009061:Mouth Mucosa / Q000166:cytology / Q000378:metabolism; D009153:Mutagens / Q000633:toxicity*; D016273:Occupational Exposure / Q000032:analysis* / Q000706:statistics & numerical data; D011110:Polymorphism, Genetic; D017132:Workplace / Q000592:standards
D015415:Biomarkers; D004268:DNA-Binding Proteins; D009153:Mutagens; C110901:X-ray repair cross complementing protein 3; D005557:Formaldehyde; D000445:Aldehyde Oxidoreductases; C087006:formaldehyde dehydrogenase, glutathione-independent