# DNA CONTENT OF DYSPLASTIC LESIONS IN HUMAN AND RAT LIVER

> **NIH NIH R01** · CASE WESTERN RESERVE UNIVERSITY · 1990 · $170,810

## Abstract

We have found, by cytospectrophotometric methods, that a small number of
rat liver nodules induced by an initiation-promotion regimen have an
aneuploid modal DNA content.  Over the past two years we have not only
confirmed the initial finding, but also determined that aneuploidy is
present when either choline deficiency or phenobarbital are given
separately after the same initiation treatment with diethylnitrosamine.  We
now have preliminary evidence, which will have to be validated in future
experiments, that the administration of diethylnitrosamine alone or the
feeding of a choline deficient diet by itself produces aneuploidy in some
enzyme altered foci.  The quantitative alterations in the genome that
result in aneuploidy are in fact a manifestation of the PROGRESSION stage
during transformation into malignancy.  Since aneuploidy results in a
heterogeneous cell population, the subsequent ability of some tumors to
metastasize may have been decided at the beginning of the carcinogenic
process and not later, as a consequence of changes that follow overt
malignancy.

Cytospectrophotometry is a grudging, slow methodology.  The advent of
Computerized Digital Image Analysis, together with the complete automation
of the system we propose in this application, should overcome most of these
problems.

The second phase of our investigations will be at first devoted mostly to
the originally planned experiments to study the relationship between ploidy
distribution, nodule persistence and hepatoma development.  Treatment of
these animals has already been performed in the first funding cycle.  With
the use of Computerized Image Analysis we will also determine whether
aneuploidy is seen with either promoting treatment or with
diethylnitrosamine when each is applied separately.  In the last part of
our studies we will examine, using the same methodology, whether aneuploidy
is caused by clastogenic changes due to the administration of methyl-N-
nitros-urea/phenobarbital or aflatoxin B1/phenobarbital or by agents that
produce abnormal or arrested mitotic spindles, such as diethylstilbestrol.

The experiments proposed will help to understand the mechanisms of
PROGRESSION in the rat liver in vivo (as opposed to cells in culture) and
may result in less restrictive but more veritable regulations for in vivo
tests of hepatocarcinogenesis.

## Key facts

- **NIH application ID:** 3172940
- **Project number:** 5R01CA035362-05
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **SAM.gov UEI:** HJMKEF7EJW69
- **Principal Investigator:** OSCAR SUDILOVSKY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1990
- **Award amount:** $170,810
- **Award type:** 5
- **Project period:** 1985-04-01 → 1992-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3172940

## Citation

> US National Institutes of Health, RePORTER application 3172940, DNA CONTENT OF DYSPLASTIC LESIONS IN HUMAN AND RAT LIVER (5R01CA035362-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3172940. Licensed CC0.

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