Bile-salt induction of apoptosis in human lymphoid and colonic epithelial cells: Relevance to colon cancer.
AuthorSamaha, Hanan El-Sayed Taha.
Committee ChairBernstein, Harris
MetadataShow full item record
PublisherThe University of Arizona.
RightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
AbstractDeath from cancer of the colon is the third leading cause of cancer death in the United States. Epidemiologic evidence indicates that life style factors and particularly a high fat western diet play an important role in colon cancer. Cheah (1990) concluded that bile salts present in the feces as the result of a high fat diet are the most important etiologic agent in colon cancer. The mechanism of action of bile salts, however, is largely unknown. Bile salts have been shown to cause DNA damage in some mammalian cell types. As a first line of defence, the cell ordinarily attempts to repair the DNA damage. However, failure to repair damage can lead the cell to commit suicide (apoptosis). Apoptosis is an active physiologic mode of cell death. In this study, apoptosis was detected using Wright-stained cytospins for lymphoid cells and one micron, plastic-embedded sections for colonic epithelial cells using the light microscope. I examined the effect of the bile salt sodium deoxycholate (NaDOC) on three types of cells: transformed human lymphocytes, normal human mononuclear cells and colonic epithelial cells. I found that NaDOC induces apoptosis in lymphoid cells. This might decrease the number of lymphocytes available to defend against mutant colonic epithelial cells that develop into tumors. Also I found that NaDOC induces apoptosis in colonic goblet cells. This induction of apoptosis was strong in colon epithelial cells from normal individuals or polyp patients at low risk for colon cancer. However, the goblet cells of the apparently normal mucosa from colon cancer patients (and polyp patients at high risk for colon cancer) were found to be relatively resistant to the apoptosis-inducing effect of NaDOC. To explain these results the following model was proposed. Under conditions of a high fat diet, bile salts, may select for a population of apoptosis-resistant cells. This may lead to repopulation of the colon with cells that do not respond to DNA damage by entering the apoptosis pathway. Rather, these cells may replicate and undergo mutation at the sites of the DNA damage. These mutations may contribute to colon carcinogenesis.
Degree ProgramNutritional Sciences