# BIOCHEMICAL TOXICITY OF AGENTS INCREASING REACTIVE 02

> **NIH NIH R01** · INSTITUTE FOR CANCER PREVENTION · 1990 · $149,633

## Abstract

In this renewal application, research is proposed to elucidate the
toxicologic mechanism(s) for the liver carcinogenicity of certain
peroxisome-proliferating agents (PPA).  The dominant hypotherical
mechanism, for which there is substantial supporting evidence, is
that these agents increase cellular levels of H2O2 leading to
macromolecular damage and cellular alteration.  During the previous
grant period, we were unable to obtain direct confirmation for this
sequence, but further experiments are proposed to examine the
hypothesis in a rigorous manner.  Findings in the preceding
research also lead us to consider additional mechanisms, which may
operate independent of oxidative damage or in conjunction with it.
The specific aims for the contimued research are as follows:  (1)
Identify two genetically-defined groups of mice and a PPA most
likely to show differences in PPA-induced tumorigenesis, assuming
the H2O2 hypothesis to be true and delineate the dose-response
effects of that PPA on tumorigenesis in those two groups;  (2)
Investigate PPA-induced oxidative damage on liver cell
macromolecules and; (3)  Investigate PPA-induced liver cell
proliferation as a mechanistically important event in PPA
carcinogenicity.

## Key facts

- **NIH application ID:** 3178650
- **Project number:** 5R01CA039545-05
- **Recipient organization:** INSTITUTE FOR CANCER PREVENTION
- **Principal Investigator:** GARY M WILLIAMS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1990
- **Award amount:** $149,633
- **Award type:** 5
- **Project period:** 1985-12-01 → 1991-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3178650

## Citation

> US National Institutes of Health, RePORTER application 3178650, BIOCHEMICAL TOXICITY OF AGENTS INCREASING REACTIVE 02 (5R01CA039545-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3178650. Licensed CC0.

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