| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Carcinogenesis |
Laboratories of Cellular and Molecular Biology [E. M., M. K. E.] and Molecular Gerontology [S. G. N., V. A. B.], National Institute on Aging National Institutes of Health, Baltimore, Maryland 21224
Breast cancer is one of the major causes of mortality among women in the United States. Although the causes of breast cancer remain unclear, it has been speculated that DNA base damage may lead to mutations that subsequently can be carcinogenic. Recently, defective oxidative DNA damage repair has been implicated in breast tumorigenesis. The major oxidative DNA lesion, 8-hydroxyguanine (8-oxoG), is increased in breast cancer, suggesting that this lesion may play a crucial role in the etiology of breast cancer. However, it is not known whether the repair of 8-oxoG or other oxidative base lesions is altered during breast carcinogenesis. We examined the ability of nuclear and mitochondrial extracts of two human breast cancer cell lines, MCF-7 and MDA-MB-468, to repair 8-oxoG lesion. We report that mitochondrial extracts from the two breast cancer cell lines are defective in the base excision repair of 8-oxoG relative to two noncancer cell lines. We also show that the incision activity of 8-oxoG was significantly lower in mitochondrial than in nuclear extracts in the breast cancer cell lines. The defective mitochondrial repair activity was not attributable to lower levels of human 8-hydroxyguanine DNA glycosylase, the base excision repair enzyme known to incise 8-oxoG in DNA. The repair of thymine glycol, another major oxidative DNA base lesion that blocks transcription and causes cell death, was similar in cancer and noncancer cells. Furthermore, nuclear extracts incised thymine glycol with a much higher efficiency than 8-oxoG. These data provide evidence for defective repair of 8-oxoG in mitochondria of MCF-7 and MDA-MB-468 breast cancer cell lines. These results may implicate 8-oxoG repair mechanisms in mitochondria of certain breast cancers.
This article has been cited by other articles:
|
|
 |
|
  S. Maynard, S. H. Schurman, C. Harboe, N. C. de Souza-Pinto, and V. A. Bohr Base excision repair of oxidative DNA damage and association with cancer and aging Carcinogenesis, January 1, 2009; 30(1): 2 - 10. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-K. Youn, P. I. Song, M.-H. Kim, J. S. Kim, J.-W. Hyun, S.-J. Choi, S. P. Yoon, M. H. Chung, I.-Y. Chang, and H. J. You Human 8-Oxoguanine DNA Glycosylase Suppresses the Oxidative Stress Induced Apoptosis through a p53-Mediated Signaling Pathway in Human Fibroblasts Mol. Cancer Res., October 1, 2007; 5(10): 1083 - 1098. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. W. Hill and M. K. Evans Dimerization and opposite base-dependent catalytic impairment of polymorphic S326C OGG1 glycosylase Nucleic Acids Res., March 20, 2006; 34(5): 1620 - 1632. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. R. Trzeciak, S. G. Nyaga, P. Jaruga, A. Lohani, M. Dizdaroglu, and M. K. Evans Cellular repair of oxidatively induced DNA base lesions is defective in prostate cancer cell lines, PC-3 and DU-145 Carcinogenesis, August 1, 2004; 25(8): 1359 - 1370. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Jensen, G. Calvayrac, B. Karahalil, V. A. Bohr, and T. Stevnsner Mammalian 8-Oxoguanine DNA Glycosylase 1 Incises 8-Oxoadenine Opposite Cytosine in Nuclei and Mitochondria, while a Different Glycosylase Incises 8-Oxoadenine Opposite Guanine in Nuclei J. Biol. Chem., May 23, 2003; 278(21): 19541 - 19548. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
