# GAMMA-GLUTAMYLTRANSPEPTIDASE NEGATIVE HEPATOCARCINOGEN-

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 1988 · $169,128

## Abstract

Severaal structurally different hypolipidemic compounds and
certain phthalate ester plasticizers, the two classes of peroxisome
proliferators (PPs) induce, altered areas, neoplastic nodules, and
hepatocellular carcinomas in rats and mice after chronic dietary
administrtaion.  The phenotypic properties of hepatic lesions
induced by PPs are signifcantly different from those induced by
classical carcinogens.  Based on these differences we hypothesize
a possible divergence in the mechanism of action by which
nomutagenic PPs and classical carcinogens induce liver tumors.
We propose that these differences are probably due to a field
effect of highly electrophilic reactans of classical carcinogens
affecting a variety of genes, whereas the PPs, which probably act
by a receptor mediated mechanism, alter the expression of a
highly selected set of genes.  The specific aims are:  1)
Comparative evaluation of the biologic properties of hepatic
lesions in the rat induced by 2 structurally different hypolipidemic
peroxisome proliferators, Wy-14,643 and ciprofibrate with those
induced by a classical carcinogen by evaluation of:  a) phentypic
properties, b) functional properties of AA, NN and HCC, and c)
autonomous growth properties of AA and NN in the host livers
after discontinuation of PP treatment and after transplantaton
into syngeneic rats.  2) Examination of NN and HCC induced by
PPs, Wy-14,643 and ciprofibrate, and those induced by a classical
carcinogen for the expression of genes coding for albumin, alpha-
feto-protein, catalase, enzymes of peroxsomal beta-oxidation
system, selected phase II drug detoxifying enzymes, DT-
diaphorase and epoxide hydrolase by a) measuring mRNA levels
using specific cDNA probes, b) examining methylation pattern of
AFP, albumin and beta-oxidation enzymes genes using methylation
sensitive restriction enzymes, and c) evaluating the amplification
of beta-exidation enzyme genes.  3) Examination of Nn and HCC
induced by classical genotoxic carcinogens and PPs for
differences in the expression of oncogenes compared to one
another and to the surrounding normal liver using northern blot
analysis and by in situ hybridiation.  4) Identification of
oncogene(s) in DNA of HCC induced by PPs using NIH 3T3 cell
transformation assay and determination of the mechanism by
which they have been activated.  5) Further characterization of
HCC of different degree of differentiation and examine for
morphological functional properties after a) developing of
transplantable tumors, and b) establishing cell lines.

## Key facts

- **NIH application ID:** 3173632
- **Project number:** 2R01CA036130-04
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **SAM.gov UEI:** KG76WYENL5K1
- **Principal Investigator:** SAMBASIVA M RAO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $169,128
- **Award type:** 2
- **Project period:** 1984-07-01 → 1990-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3173632

## Citation

> US National Institutes of Health, RePORTER application 3173632, GAMMA-GLUTAMYLTRANSPEPTIDASE NEGATIVE HEPATOCARCINOGEN- (2R01CA036130-04). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3173632. Licensed CC0.

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