In dismutase and catalase dictates the deleterious

In a similar way, various
antioxidants also have a significant effect on arsenic-induced genotoxicity. The balance between the rate of generation of
free radicals and the rate of their removal by various antioxidant enzymes such
as superoxide dismutase and catalase dictates the deleterious effect of
oxidative stress. Enzymes like superoxide dismutase and catalase are capable of
partially suppressing both the toxicity and the mutagenic potential of sodium
arsenite by catalyzing the dismutation of superoxide anions and by preventing
the formation of hydroxyl radicals via removal of hydrogen peroxide respectively. On the other hand, no protection
was offered by heat-inactivated catalase treatment.

Therefore catalase and
SOD are capable of reducing the mutagenic potential of arsenic. This is also
consistent with other data obtained including the ability of sodium arsenite to
induce heme oxygenase, an oxidative stress protein, and peroxidase in various
human cell lines. Moreover, the arsenite-induced
occurrence of sister chromatid exchanges was reduced by antioxidant
enzymes such as SOD in cultured human lymphocytes.

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It is known that arsenic
induces hydrogen peroxide which is a precursor of hydroxyl radicals in AL
cells. Even though SOD (30 kDa) and
catalase (250 kDa) cannot diffuse across the membrane without being phagocytosed due to the relatively large size,
hydrogen peroxide can. Even though the
exact pathway is not known, the addition of extracellular antioxidants can
reduce the intracellular oxidative stress induced by arsenite treatment and
suppress the mutagenicity of arsenic in mammalian cells and reduced subsequent
genotoxic damage.

Arsenic was capable of
inducing specific DNA lesions consistent with oxidative damage like
8-hydroxy-2V-deoxyguanosine (8-OHdG) generation. Arsenic treatment (4 Ag/ml for
24 h) was shown to increases the level of 8-OHdG in AL cells by more than
2-fold when compared to non-treated controls as evidenced by antibody staining.
Moreover, the addition of SOD and
catalase was capable of reducing this increase by 75%. Moreover, 8-OHdG has also been detected in the skin of patients
with arsenic-related Bowen’s disease and in the liver of rats exposed to DMAV. These results indicate that ROS generation is a
major pathway for Arsenic-mediated genotoxicity in mammalian cells.

 In mouse
lung tissue, reduced expression of proteins associated with cellular migration
was observed when exposed to low dose of arsenic, as evidenced by
high-throughput protein screening experiments. In addition to this alteration
of a specific wound repair protein, marker was also observed in mouse
bronchoalveolar fluid. On lung tissue of mice fed low-dose arsenic, changes in
extracellular matrix (ECM) protein expression and a large increase in matrix
metalloproteinase (MMP)-9 expression was revealed as seen in microarray
experiments. MMPs are responsible for ECM degradation among other proteolysis. MMP-9 is the most
prominently studied MMP in the lung and has been associated with a variety of
lung diseases. An increase in the ratio of MMP-9 to tissue inhibitor of matrix
metalloproteinase (TIMP)-1 in collected sputum samples of humans were observed
under low-level arsenic exposure. This imbalance between MMP-9 and TIMP-1 can
cause changes in epithelial wound response, thereby contributing to the
progression of airway remodeling. Altered wound response is partly due to
increased secretion and activity, as arsenic concentration increases. Moreover,
an increase in arsenic concentration inhibits the ability for 16HBE14o- cells
to repair monolayers in culture. To conclude, arsenic is 

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