# MECHANISMS OF INHIBITION OF CHEMICAL CARCINOGENESIS

> **NIH NIH R01** · OREGON STATE UNIVERSITY · 1993 · $173,183

## Abstract

Our overall aims are to elucidate anticarcinogenic mechanisms for selected
blocking to better evaluate the potential impact of such dietary factors
on human Aim 2 focuses on anti-initiation mechanisms, with initial emphasis
on the common dietary factors indole-3-carbinol (I3C) and chlorophylls.
Aim 1 addresses the almost total lack of truly quantitative information on
the relationship between inhibitor dose and carcinogen potency (i. e. TD50
value), or whether inhibitor effects at high carcinogen dose and tumor
response apply at lower doses and incidences more reflective of human
cancer.  We address these issues through 9000-animal molecular dosimetry
tumor studies that quantify relationships between carcinogen dose,
modulator dose, altered DNA adduction, and final tumor outcome as reflected
in inhibitor-altered TD50 values.  The data thus determine if reduced DNA
adduction alone quantitatively accounts for, and predicts, reduced tumor
outcome, and also measure "percent inhibition" vs. inhibitor dietary
concentration.  Unfortunately, in some protocols many "anticarcinogens"
show co-carcinogenesis or promotion, or are limited by a low
potency/toxicity ratio.  Aims 1 and 3 investigate tumor dose-response and
DNA adduction relationships for such agents, and examine combined
chemoprevention protocols to overcome some of these limitations.  We also
address a common shortcoming in previous combined inhibitor studies, which
lack any statistical measure of synergism or antagonism.  Much of our
proposed work uses I3C as a model natural blocking agent that also can
promote.  We believe it fundamentally important to understand mechanisms
of such ambivalent factors, and to derive dose-response approaches to
quantify relative inhibitory benefit vs. promotional risk.  Finally, Aim
4 proposes tumor modulation studies using 3 new dietary factors, to
modestly expand the data base beyond rodent models for future comparative
mechanism studies.  Our animal model, the rainbow trout, has unique value
for the proposed studies for two principal reasons: 1) comparative
mechanism studies are essential for confidant extrapolation of relevant
inhibitory mechanisms to humans, and 2) the economies and sensitivity of
the model permit a great range and complexity in tumor study design, which
allows us to approach fundamental concepts of anticarcinogenesis of high
statistical demand at a relatively modest budget. Many of our proposed
experiments would be economically unrealistic, and in the case of rare
carcinogens or modulators, not feasible with rodent models.

## Key facts

- **NIH application ID:** 3172512
- **Project number:** 5R01CA034732-10
- **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:** 1993
- **Award amount:** $173,183
- **Award type:** 5
- **Project period:** 1983-05-01 → 1995-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3172512

## Citation

> US National Institutes of Health, RePORTER application 3172512, MECHANISMS OF INHIBITION OF CHEMICAL CARCINOGENESIS (5R01CA034732-10). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3172512. Licensed CC0.

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