# MECHANISMS OF INHIBITION OF CHEMICAL CARCINOGENESIS

> **NIH NIH R01** · OREGON STATE UNIVERSITY · 1987 · $128,631

## Abstract

The overall aim is to enhance our understanding of the mechanisms of
anti-carcinogenesis by synthetic and naturally occurring compounds, and
their possible impact on human cancer.  This becomes especially important
in view of the results from our laboratory and others that some putative
food-borne inhibitors in the human diet actually enhance tumor response
experimentally.  Much of the work will use a component of brassica
vegetables, indole-3-carbinol (I3C), as a model for blocking agents which
can also promote.  We will use the rainbow trout, which has proven
responsive to a number of carcinogens and inhibitors, and is especially
valuable for inhibitor studies for three reasons:  a) Mechanism studies in
this non-mammalian vertebrate broadens our data base for extrapolation to
man; b) Its economies and sensitivity permit a great range of tumor studies
for investigating fundamental concepts of anti-carcinogenesis at modest
cost.  Many of the proposed studies would be economically unrealistic, or
unfeasible for rare metabolites, in traditional rodent models.  c) Use of
alternative vertebrates where sound and feasible reduces use of mammalian
test animals.  Specific aims are:  1) Conduct tumor studies using aflatoxin
B1 (AFB1) and two selected inhibitors, to rigorously establish the
relationships between applied carcinogen dose, inhibitors, to rigorously
establish the relationships between applied carcinogen dose, inhibitor
dose, peak target tissue DNA adduct formation, and final tumor response in
trout.  2) Investigate and quantitate changes in responsiveness to tumor
inhibitors with increasing age, and the role of altered carcinogen
pharmacokinetics, metabolism, and DNA adduct formation in this process.  3)
Extend previous investigations into the detailed mechanisms of 13C
inhibition of AFB1 carcinogenesis.  Synthesize radiolabeled 13C and
investigate its metabolism in vivo and in isolated cells.  Where possible
test metabolite(s) for ability to alter carcinogen metabolism and inhibit
DNA adduct formation.  Determine I3C effects on specific trout hepatic and
intestinal phase III detoxifying activites.  4) Investigate mechanisms of
promotion by 13C and quantitatively assess its potencies for promotion
versus inhibition.  Conduct structure/function tumor studies for promotion
or inhibition by 13C analogues.  Determine 13C effects on target cell
proliferation, ornithine decarboxylase activity, intercellular
communication, and/or DNA damage.  5) Expand the data base of
inhibitor/carcinogen testing in the trout model, each with specific
rationale under test, using protocols which detect promotion or
inhibition.  Initiate mechanism studies where inhibition or promotion occur.

## Key facts

- **NIH application ID:** 3172508
- **Project number:** 5R01CA034732-05
- **Recipient organization:** OREGON STATE UNIVERSITY
- **SAM.gov UEI:** MZ4DYXE1SL98
- **Principal Investigator:** GEORGE S BAILEY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $128,631
- **Award type:** 5
- **Project period:** 1983-05-01 → 1990-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3172508

## Citation

> US National Institutes of Health, RePORTER application 3172508, MECHANISMS OF INHIBITION OF CHEMICAL CARCINOGENESIS (5R01CA034732-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3172508. Licensed CC0.

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