Details:

Alternative Title:
Biomed Res Int
Personal Author:
Stephenson, Adrienne P. ; Mazu, Tryphon K. ; Miles, Jana S. ; Freeman, Miles D. ; Reams, R. Renee ; ... More +
Stephenson, Adrienne P. ; Mazu, Tryphon K. ; Miles, Jana S. ; Freeman, Miles D. ; Reams, R. Renee ; Flores-Rozas, Hernan Less -
Description:
Manganese (Mn) is essential for normal physiologic functioning; therefore, deficiencies and excess intake of manganese can result in disease. In humans, prolonged exposure to manganese causes neurotoxicity characterized by Parkinson-like symptoms. Mn(2+) has been shown to mediate DNA damage possibly through the generation of reactive oxygen species. In a recent publication, we showed that Mn induced oxidative DNA damage and caused lesions in thymines. This study further investigates the mechanisms by which cells process Mn(2+)-mediated DNA damage using the yeast S. cerevisiae. The strains most sensitive to Mn(2+) were those defective in base excision repair, glutathione synthesis, and superoxide dismutase mutants. Mn(2+) caused a dose-dependent increase in the accumulation of mutations using the CAN1 and lys2-10A mutator assays. The spectrum of CAN1 mutants indicates that exposure to Mn results in accumulation of base substitutions and frameshift mutations. The sensitivity of cells to Mn(2+) as well as its mutagenic effect was reduced by N-acetylcysteine, glutathione, and Mg(2+). These data suggest that Mn(2+) causes oxidative DNA damage that requires base excision repair for processing and that Mn interferes with polymerase fidelity. The status of base excision repair may provide a biomarker for the sensitivity of individuals to manganese.
Subjects:
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Alleles Antioxidants DNA Repair Magnesium Manganese Mutation Mutation Rate Phenotype Saccharomyces Cerevisiae
Source:
Biomed Res Int. 2013; 2013.
Pubmed ID:
24282812
Pubmed Central ID:
PMC3825218
Document Type:
Journal Article
Funding:
2 G12 RR003020/RR/NCRR NIH HHS/United States ; 3U50TS473408-05W1/TS/ATSDR CDC HHS/United States ; 5S11ES01187-05/ES/NIEHS NIH HHS/United States ; 8 G12 MD007582-28/MD/NIMHD NIH HHS/United States ; G12 MD007582/MD/NIMHD NIH HHS/United States
2 G12 RR003020/RR/NCRR NIH HHS/United States ; 3U50TS473408-05W1/TS/ATSDR CDC HHS/United States ; 5S11ES01187-05/ES/NIEHS NIH HHS/United States ; 8 G12 MD007582-28/MD/NIMHD NIH HHS/United States ; G12 MD007582/MD/NIMHD NIH HHS/United States Less -
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:6065748260c0987fea42910abc27eb1a848608950bacaa3cd7c96848d8544df5
Download URL:
https://stacks.cdc.gov/view/cdc/22548/cdc_22548_DS1.pdf
File Type:

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