Graduate Thesis Or Dissertation
 

Modulation of chemically-induced hepatocarcinogenesis by indole-3-carbinol : mechanisms and species comparison

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https://ir.library.oregonstate.edu/concern/graduate_thesis_or_dissertations/xk81jn852

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  • There is plenty of evidence from epidemiology studies supporting a link between certain components in the human diet and cancer incidence. It is estimated that 3-4 million annual cases of cancer could be prevented worldwide just by changing dietary habits. In parts of the world where vegetables and fruits constitute a large part of the diet, certain cancer incidences are markedly lower compared to Western countries. In particular, consumption of cruciferous vegetables is negatively associated with occurrence of certain cancers. One of the compounds from crucifers that is implicated in chemoprevention, is indole-3-carbinol(I3C), documented to inhibit tumor formation in several tissues in rodents, including the mammary tissue. I3C and is currently being evaluated in several clinical trials as a chemopreventive agent against breast cancer in humans. There are, however, some legitimate concerns regarding the use of Pure I3C since, depending upon conditions of administration, I3C can act as a promoter of hepatocarcinogenesis. Evidence is presented here that dietary I3C can promote and/or enhance liver tumor formation in rainbow trout (supporting earlier reports in literature) and the C57BL/6J mouse (enhancement in short-term pre-initiation exposure through lactational transfer, inhibition in a long-term post-initiation feeding study). I3C is also reported to promote in the rat liver model. A major concern associated with dietary I3C supplementation relates to its estrogenic effects as seen in trout and also its ability to induce certain cytochrome P-450s involved in procarcinogen activation. Biological effects of I3C are attributed to its acid condensation products. It was observed in this study that I3C acts through different mechanisms, including the Ah receptor-mediated and estrogenic pathways. Understanding of the role of I3C derivatives in beneficial and/or hazardous effects resulting from dietary exposure will be crucial in evaluating the promise of I3C as a chemoprevention agent. Questions pertaining to the risk/benefit of the use of dietary I3C supplementation for preventing estrogen-related diseases, without increasing the risk of promotion of hepatocarcinogenesis in humans, may depend on whether the mechanism(s) of action of I3C derivatives in humans is more like the adult mouse or the neonatal mouse, rat and trout.
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