# MODIFICATION OF PEROXISOME PROLIFERATOR CARCINOGENESIS

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 1988 · $124,375

## Abstract

The overall objective of the proposed research on the modification of
peroxisome proliferator-induced hepatocarcinogenesis is to enhance our
present understanding of the mechanism(s) of carcinogenesis by
di-(2-ethylhexyl) phthalate (DEHP), a widely used industrial phthalate
ester plasticizer, and certain hypolipidemic agents such as ciprofibrate,
which constitute two very important classes of peroxisome proliferators.
Peroxisome proliferators exert unique biological and biochemical
alterations in liver.  These include profound proliferation of the
cytoplasmic organelle peroxisome and increase in H202 generating
peroxisomal long-chain fatty acid Beta-oxidation enzyme system.  Since
these chemicals are non-mutagenic, non-DNA damaging, and do not form
adducts with DNA, it is suggested that their carcinogenicity is due to
sustained proliferation of peroxisomes leading to excess generation of H202
and other active oxygen species.  The proposed studies of modification of
peroxisome proliferator carcinogenesis with antioxidants (vitamin E, and
ethoxyquin) and with high-dietary fat should generate new information
regarding the role of lipid peroxidation and antioxidants in liver
carcinogenesis.  This proposal includes studies on:  1) the effect of
antioxidant ethoxyquin on carcinogenesis by DEHP; 2) the role of dietary
vitamin E on inhibiting peroxisome proliferator carcinogenesis; 3) the role
of dietary fat on enhancing peroxisome proliferator carcinogenesis; 4) the
effect of ethoxyquin on cell proliferation and growth of putative
preneoplastic lesions in liver induced by a peroxisome proliferator; and 5)
the effect of ethoxyquin on DNA repair and alterations in protein synthesis
and certain enzymes in liver induced by a peroxisome proliferator.  It is
anticipated that antioxidants may prove useful for individuals who are
exposed to phthalate ester plasticizers and those requiring continued use
of anti-hyperlipidemic drugs.

## Key facts

- **NIH application ID:** 3170398
- **Project number:** 5R01CA032504-06
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **SAM.gov UEI:** KG76WYENL5K1
- **Principal Investigator:** JANARDAN K. REDDY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $124,375
- **Award type:** 5
- **Project period:** 1982-05-01 → 1989-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3170398

## Citation

> US National Institutes of Health, RePORTER application 3170398, MODIFICATION OF PEROXISOME PROLIFERATOR CARCINOGENESIS (5R01CA032504-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3170398. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*