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. / Graduation date: 1998
| Identifer | oai:union.ndltd.org:ORGSU/oai:ir.library.oregonstate.edu:1957/33712 |
| Date | 25 November 1997 |
| Creators | Oganesian, Aram |
| Contributors | Williams, David E. |
| Source Sets | Oregon State University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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