# INHIBITION OF CHEMICAL CARCINOGENESIS BY INTERFERON

> **NIH NIH R01** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 1988 · $124,844

## Abstract

The cytochrome P-450 mixed-function monooxygenase system (MFO) is involved
in the metabolism of xenobiotics and carcinogens.  Interferon (IFN)
inducers and preparations decrease hepatic cytochrome P-450 levels and
suppress the induction of the MFO system by 3-methylcholanthrene (3-MC) and
phenobarbitol (PB).  Some of the major objectives of this proposal are:  1)
determine whether IFN inducer-dependent effects on the P-450 system are
mediated by IFNs; 2) determine whether the various P-450 cytochromes are
equally susceptible to IFN-dependent effects, and whether the different
classes of IFNs (Alpha, Beta, Gamma) have differential effects on the P-450
cytochromes; 3) survey the effects of IFNs on P-450 mRNA synthesis; and 4)
analyze the contribution of the IFN-dependent induction of xanthine oxidase
(XO) to the modulation of the MFO system.  Mice will be treated in vivo
with IFN inducers or preparations (IFN-Alpha, Beta or Gamma) and the
kinetics of overall P-450 loss and recovery will be determined in liver
homogenates.  Specific monooxygenase assays and immunoblot analyses of
P-450 polypeptides separated on SDS acrylamide gels and probed with P-450
antibodies will be used to determine effects on specific P-450 species.
Hybridization analyses with fragments complementary to specific 3-MC and PB
inducible P-450 mRNAs will be used to determine IFN effects on P-450 mRNA
transcription and processing.  Allopurinol, an inhibitor of XO, will be
used to determine whether the IFN-dependent induction of XO is responsible
for modulating the MFO system.

Since reactive oxygen species have been implicated in tumor promotion, the
IFN-dependent induction of XO, which produces reactive oxygen species,
suggests that IFNs might have "promoter-like" activities.  The additional
objectives of the proposal are:  5) to survey in murine skin and cultured
keratinocytes the effects of IFNs on a variety of biochemical and
morphological markers associated with the promotion stage of chemical
carcinogenesis in murine skin; and 6) determine whether IFNs can
coordinately moduclated enzymes (superoxide dismutase, catalase, and
glutathione peroxidase) involved in the detoxification of reactive oxygen
species.  Allopurinol will be used in some studies to evaluate whether the
IFN-dependent induction of XO is responsible for IFN "promoter-like"
properties.

## Key facts

- **NIH application ID:** 3172186
- **Project number:** 5R01CA034469-06
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **SAM.gov UEI:** S3GMKS8ELA16
- **Principal Investigator:** JOHN J REINERS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $124,844
- **Award type:** 5
- **Project period:** 1983-09-01 → 1991-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3172186

## Citation

> US National Institutes of Health, RePORTER application 3172186, INHIBITION OF CHEMICAL CARCINOGENESIS BY INTERFERON (5R01CA034469-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3172186. Licensed CC0.

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