Antioxidants prevent oxidative DNA damage and cellular transformation elicited by the over-expression of c-MYC Journal Article
| Authors: | Sagun, K. C.; Cárcamo, J. M.; Golde, D. W. |
| Article Title: | Antioxidants prevent oxidative DNA damage and cellular transformation elicited by the over-expression of c-MYC |
| Abstract: | Reactive oxygen species (ROS)-induced genomic damage may have important consequences in the initiation and progression of cancer. Deregulated expression of the proto-oncogene c-MYC is associated with intracellular oxidative stress and increased DNA damage. However, the protective role of antioxidants such as Vitamin C against MYC-induced genomic damage has not been fully investigated. In a variety of cell lines, we show that ectopic MYC over-expression results in the elevation of intracellular ROS levels and a concomitant increase in oxidative DNA damage, as assessed by levels of 8-oxo-7,8-dihydro-2′- deoxyguanosine (8-oxo-dG) in the genomic DNA. Loading cells with ascorbic acid (AA) relieved MYC-elicited intracellular oxidative stress and conferred genomic protection. A mitochondrially targeted Vitamin E analog, TPPB, also protected cells from MYC-elicited oxidative DNA damage, suggesting the involvement of mitochondria in increased ROS production. We found that deregulated MYC expression resulted in the attenuation of intracellular glutathione levels, which was reversed by loading cells with Vitamin C. Additionally, cells over-expressing MYC had elevated levels of intracellular superoxide, which was significantly quenched by Vitamin C or the selective superoxide quencher, Tiron. Consequently, Vitamin C and other antioxidants protected cells from MYC-induced cellular transformation. Our studies implicate a role for ROS, and superoxide in particular, in MYC-elicited oxidative DNA damage and cellular transformation, and point to a pharmacological role of antioxidants in cancer chemoprevention. |
| Keywords: | controlled study; human cell; cancer growth; nonhuman; animal cell; animals; mice; dna damage; gene expression; cell line; hela cell; animalia; cell transformation, neoplastic; gene expression regulation; cell transformation; genes, myc; reactive oxygen metabolite; rats; antioxidant; oxidative stress; antioxidants; alpha tocopherol; ascorbic acid; oncogene c myc; superoxide; superoxides; mitochondria; glutathione; 8 hydroxydeoxyguanosine; ros; 8-oxo-dg; foci; vitamin c; tiron |
| Journal Title: | Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis |
| Volume: | 593 |
| Issue: | 1-2 |
| ISSN: | 0027-5107 |
| Publisher: | Elsevier Science, Inc. |
| Date Published: | 2006-01-01 |
| Start Page: | 64 |
| End Page: | 79 |
| Language: | English |
| DOI: | 10.1016/j.mrfmmm.2005.06.015 |
| PUBMED: | 16085125 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 9" - "Export Date: 4 June 2012" - "CODEN: MRFME" - "Source: Scopus" |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work