Satya Narayan, Ph.D.
Associate Professor
Department of Anatomy and Cell Biology and UF Shands Cancer Center

Cigarette smoke can turn normal breast cells cancerous by blocking their ability to repair damaged DNA. In the past several years evidence has been provided that various molecular mechanisms resulting in genomic instability play an important role in human carcinogenesis. Once a normal cell is challenged with DNA-damaging agent, two possibilities arise immediately within the cell. First, the cell can use its DNA repair machinery and fix the damaged DNA. Second, if the DNA repair machinery of the cell is compromised, then the accumulation of multiple genetic mutations may occur. The consequence of the accumulation of mutations in a susceptible cell may lead to the perturbation of regulatory network(s) that controls proliferation, survival, and cellular function, and ultimately results in cancer. Cigarette smoke contains about 4,000 chemicals and many of them of are well-known carcinogens or DNA-damaging agents. However, whether cigarette smoking is related to breast carcinogenesis is not well established.

Several epidemiological studies have examined the relationship between smoking and breast cancer risk and showed negative, positive or null association between smoking and breast malignancies. Previous experimental studies showed a link with cigarette smoking with breast carcinogenesis but were limited with the use of a single chemical component of the cigarette smoke. Our studies instead used cigarette smoke condensate, a surrogate for cigarette smoke that contains all of the 4,000 chemicals found in cigarette smoke. In our studies, we showed the transformation of normal human breast epithelial cells in culture after treatment with cigarette smoke condensate. We found that cigarette smoke condensate can cause DNA damage and induce levels of adenomatous polyposis coli (APC) in challenged normal human breast epithelial cells. The induced levels of APC interact with DNA polymerase beta, block DNA polymerase beta-mediated DNA repair, and compromise DNA repair capacity of cells. The compromised DNA repair capacity can be detrimental for the normal breast epithelial cells and can lead to transformation or carcinogenesis. These studies were funded by the National Institutes of Health and the Miami-based Flight Attendant Medical Research Institute and published in the journal ONCOGENE ( Advanced online publication, 21 August 2006 ; doi:10.1038/sj.onc.1209925).

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