# OXYGEN RADICAL INDUCED MALIGNANT TRANSFORMATION

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 1992 · $110,500

## Abstract

We have been interested in the relationship of chronic inflammation
with many of cancer.  Our hypothesis is that phagocytes, cells
important in the inflammatory process, have the ability to generate
toxic products which can damage DNA and could contribute to the
pathogenesis of cancer.  In support of this hypothesis, we
demonstrated that normal human phagocytes can produce mutations in
bacteria and hamster cells (CHO cells), sister chromatid exchanges
(SCEs) in CHO cells, and malignant transformation of C3H lOT1/2
cells.  Further study of the mechanisms leading to these phenomena
revealed that phagocyte-generated toxic oxygen metabolites
(including hydrogen peroxide, and the free radicals superoxide
anion and hydroxyl radical) are important in the pathogenesis of
these genetic effects.  We have also studied antioxidant mechanisms
in the prevention of the genetic damage.

While it is clear that phagocyte-generated oxidants can produce
genetic injury, the nature of the specific genetic targets critical
for transformation by this mechanism are unknown.  Recognizing that
the tumors arising from phagocyte-transformed lOT1/2 cells were a
unique resource, we have been studying oncogenes in DNA samples
prepared from these tumors.  In doing this we have found a specific
alteration in the ab1 oncogene in cells transformed by phagocyte-
generated oxidants.  In this proposal we will describe our plans
to study and elucidate this oxidant-induced ab1 oncogene
alteration.  We have also found that DNA extracted from these
Phagocyte-transformed lOT1/2 cells can cause transformation of
NIH3T3 cells after transfection.

In this proposal we describe our plan to determine the identity of
these transforming genes.

## Key facts

- **NIH application ID:** 3123449
- **Project number:** 9R01AG011536-04
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **SAM.gov UEI:** KG76WYENL5K1
- **Principal Investigator:** SIGMUND A WEITZMAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $110,500
- **Award type:** 9
- **Project period:** 1992-09-30 → 1996-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3123449

## Citation

> US National Institutes of Health, RePORTER application 3123449, OXYGEN RADICAL INDUCED MALIGNANT TRANSFORMATION (9R01AG011536-04). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3123449. Licensed CC0.

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