RESUMEN
The haloacetic acids (HAAs) are the second-most prevalent class of drinking water disinfection by-products formed by chemical disinfectants. Previous studies have determined DNA damage and repair of HAA-induced lesions in mammalian and human cell lines; however, little is known of the genomic DNA and chromosome damage induced by these compounds in primary human cells. The aim of this study was to evaluate the genotoxic and clastogenic effects of the monoHAA disinfection by-products in primary human lymphocytes. All monoHAAs were genotoxic in primary human lymphocytes, the rank order of genotoxicity and cytotoxicity was IAA > BAA >> CAA. After 6 h of repair time, only 50% of the DNA damage (maximum decrease in DNA damage) was repaired compared to the control. This demonstrates that primary human lymphocytes are less efficient in repairing the induced damage by monoHAAs than previous studies with mammalian cell lines. In addition, the monoHAAs induced an increase in the chromosome aberration frequency as a measurement of the clastogenic effect of these compounds. These results coupled with genomic technologies in primary human cells and other mammalian non-cancerous cell lines may lead to the identification of biomarkers that may be employed in feedback loops to aid water chemists and engineers in the overall goal of producing safer drinking water.
Asunto(s)
Desinfectantes/toxicidad , Desinfección/métodos , Agua Potable/química , Linfocitos/efectos de los fármacos , Mutágenos/toxicidad , Acetatos/química , Acetatos/toxicidad , Adulto , Células Cultivadas , Aberraciones Cromosómicas , Daño del ADN/efectos de los fármacos , Reparación del ADN/efectos de los fármacos , Desinfectantes/química , Humanos , Ácido Yodoacético/química , Ácido Yodoacético/toxicidad , Masculino , Índice Mitótico , Pruebas de MutagenicidadRESUMEN
The human population is heterogeneous in genetic susceptibility, chromosomal instability and disease risk; all factors which depend on inherited genetic constitution and acquired nongenetic environmental and occupational factors. Recently, special attention has been directed to the identification of sources of potential bias in population studies of gene-environment interactions including genetic admixture. The aim of this study was to evaluate the effect of genetic admixture in the association of genetic polymorphisms and chromosome aberrations (CA) in a population exposed to organic solvents. We assessed genetic admixture via 34 genetic ancestry informative markers (AIMs) in 398 Colombian individuals. We report a statistically significant difference of higher CA frequency in individuals' below-average European component, and in individuals' above-average Native American component after adjusting for covariates. In addition, the confounding risk ratio values are ≥10% than the adjusted risk ratio, suggesting that population stratification is a confounding factor in this gene-environment association study. Furthermore, after adjusting for individual admixture proportions and covariates, the results demonstrate that glutathione-S-transferase M1 (GSTM1)-null is associated with CA frequency increase. These results suggest that gene-environment association studies that involve recently admixed populations should take into consideration population stratification as a confounding factor and suggest GSTM1-null as a genetic marker associated with CA frequency increase.