Arsenic induces DNA damage via reactive oxygen species in human cells

Abstract

To elucidate arsenic-induced oxidative DNA damage, the genotoxicity of arsenic in human cells was comparatively studied with single cell gel electrophoresis (SCGE) assay in combination with the observation of the protective effects of dimethyl sulfoxide (DMSO) and catalase. Arsenic, at the concentration of 2.4 mM by coincubation for 24 hours, significantly induced DNA damage in HL60, a human promyelocytic leukemia cell line. In contrast, significant DNA damage was found in human mononucleocytes at the concentration of 4.8 mM or above. The cells were incubated separately with DMSO (12 mM/l), a well-known hydroxyl radical (OH ----) scavenger, and catalase (1,300 U/ml), a hydrogen peroxide (H 2 O 2 ) scavenger, for 6 hours and then further coincubated with various concentrations of arsenic for 24 hours at 37°°°°C and 5% CO 2 . The findings showed that both DMSO and catalase significantly reduced the arsenic-induced tail moment, a parameter of total damaged DNA, in HL60 and mononucleocytes. Hence our findings indicate that arsenic, with micromolar concentrations, induces typical and various extents of DNA damage in human cells via reactive oxygen species in a dose-dependent manner.

Formamidopyrimidine-DNA Glycosylase Enhances Arsenic-Induced DNA Strand Breaks in PHA-Stimulated and Unstimulated Human Lymphocytes

“…Other recent studies have suggested that arsenite activates NADH oxidase to produce O 2 -, which then causes oxidative DNA damage (13,24). These studies suggest that arsenic may trigger oxidative stress through multiple pathways, but H 2 O 2 and O 2 -are the main ROS involved in arsenicinduced DNA damage, as shown in our previous study (5).…”

“…Recent studies showed similar results using reactive oxygen species (ROS) scavengers such as SOD, CAT, and dimethyl sulfoxide (DMSO) to counteract mutagenicity, DNA fragmentation, and micronuclei (MN) caused by As (2)(3)(4). We observed that DMSO and CAT basically abolished most of the As-induced DNA single strand breaks (SSBs) in human cells with single-cell gel electrophoresis (SCGE) assay (5). These observations have provided indirect but powerful evidence indicating that hydrogen peroxide (H 2 O 2 ) and superoxide anion (O 2 -) are chiefly involved in the genotoxicity of As.…”

Therapeutic potential of monoisoamyl and monomethyl esters of meso 2,3-dimercaptosuccinic acid in gallium arsenide intoxicated rats

“…The antioxidant potential of DMSA has earlier been reported against arsenic (Flora, 1999) and lead (Gurer et al, 1998). Arsenic is known to induce DNA damage through mediation of reactive oxygen species (ROS) (Li et al, 2001). It is also reported that arsenic may trigger oxidative stress through multiple pathways.…”

A review on detection of heavy metal ions in water – An electrochemical approach

“…As cadmium inhibits the mismatch repair (MMR) [42,43], the cellular error gets amplified and mutations in genes become more, thereby it leads to the most dreadful cancer [29]. Cadmium can also inhibit enzymes such as superoxide dismutase (SOD) [44], catalase [45,46], glutathione peroxidase [44], glutathione reductase [45] and glutathione-S-transferase [33] and this inhibition leads to the formation of free OH radicals [47].…”

“…The toxicity mechanism of heavy metal ions is through enzyme inhibition, oxidative stress and impaired antioxidant metabolism. These mechanisms show adverse health effects through free radical generation that leads to DNA damage [28][29][30], lipid peroxidation and depletion of protein sulfhydryl [12,21]. This review highlights the few toxicity mechanisms of heavy metal ions that inhibit the enzymes and induce oxidative stress thereby affecting human health.…”