DNA Damage and Decreased DNA Repair in Peripheral Blood Mononuclear Cells in Individuals Exposed to Arsenic and Lead in a Mining Site

Abstract

The aim of this study was to evaluate DNA damage and the capacity for DNA repair in children exposed to arsenic and lead. During 2006, we studied a total of 85 healthy children (aged 4-11 years) who were residents of Villa de la Paz (community A), Matehuala (community B), and Soledad de Graciano Sanchez (community C) in San Luis Potosi, Mexico. The quantification of arsenic in urine (AsU) and lead in blood (PbB) was performed by atomic absorption spectrophotometry. The alkaline comet assay was used to evaluate DNA damage and DNA repair. The highest levels of AsU and PbB in children were found in community A (44.5 μg/g creatinine for arsenic and 11.4 μg/dL for lead), followed by community B (16.8 μg/g creatinine for arsenic and 7.3 μg/dL for lead) and finally by children living in community C (12.8 μg/g creatinine for arsenic and 5.3 μg/dL for lead). When DNA damage was assessed, children living in community A had the highest DNA damage. Analysis of these same cells 1 h after a challenge with H(2)O(2) 10 μM showed a dramatic increase in DNA damage in the cells of children living in community B and community C, but not in the cells of children living in community A. Moreover, significantly higher levels of DNA damage were observed 3 h after the challenge ended (repair period) in cells from individuals living in community A. Our results show that children exposed to metals might be more susceptible to DNA alterations.

Assessment of Arsenic Induced DNA Fragmentation by using Comet Assay

“…DNA damage has been detected in ovarian tissue in a dose-dependent manner [29]. Similarly higher extent of DNA fragmentation has also been reported in different communities of San Luis Potosi State [37] and in different schools of Mexico [36] located at different distances from arsenic smelter area.…”

“…In seven studies of human population of different arsenic contaminated areas, arsenic exposure ranged from 6 months to 18 years. Among which only in one study, the exposure time was not been reported [37]. In these seven studies significant increase has been reported in comet tail length and tail moment of exposed individuals compared to unexposed or less exposed individuals.…”

“…People of India (Murshidabad) exposed to arsenic contaminated drinking water express greater extent of DNA migration compared to unexposed population [35]. Mendez-Gomez et al [36] and Jasso-Pineda et al [37] studied different arsenic exposed areas in Mexico and observed greater fragmentation of DNA damage in areas located nearest to arsenic source (Table 2).…”

Detection of damage on single- or double-stranded DNA in a population exposed to arsenic in drinking water

“…One micromolar As is sufficient to interfere with the activity of adenosine diphosphate poly-ribose polymerase-1 (PARP-1), thereby increasing SSB and DSB fragmentation (Qin et al, 2008). Sampling of peripheral blood via venipuncture is the best way to evaluate the genotoxic effects of arsenic in exposed population in a minimally invasive way (Basu et al, 2005;Palus et al, 2005;Vuyyuri et al, 2006;Banerjee et al, 2008;Jasso-Pineda et al, 2012). The time of exposure to arsenic is an important parameter for determination of genotoxic damage.…”

Inhibition of nucleotide excision repair by arsenic

“…It is possible that repair protein expression may be lowered following chronic exposure to arsenic [45,55]; however, this mode of action cannot explain the NER repair inhibition by arsenic observed in short-term studies mentioned above.…”