# DNA SEQUENCE CHANGES DURING HEPATOCARCINOGENESIS

> **NIH NIH R01** · DARTMOUTH COLLEGE · 1988 · $107,166

## Abstract

The overall objective of this research proposal is, using
hepatocarcinogenesis as a model system, to test the hypothesis that DNA
sequence changes, including loss and rearrangement, occur during
carcinogenesis.  Specifically, we propose:  (1) to use two animal protocols
to produce liver nodules and tumors representing clonal populations of
cells at different stages in the process of hepatocarcinogenesis; (2) to
prepare a rat liver DNA probe representing minor reiterated sequence
components; (3) to determine the inter-animal and inter-strain variability
in the hybridization pattern of this probe with electropheretically
separated EcoRI digested total rat genomic DNA; (4) to compare the
hybridization patterns of the probe with electrophoretically separated
EcoRI digested genomic DNA obtained from the individual nodules and tumors
obtained in 1; (5) to determine whether hepatocarcinogenesis and/or aging
results in the loss of highly repetitive DNA sequences; (6) to determine
whether DNA isolated from hepatoma cell lines and individual liver nodules
and tumors can transform NIH 3T3 cells; and (7) to determine, using
restriction endonuclease sensitivity and mapping, whether the same or
different transforming DNA sequences are obtained from different hepatoma
cell lines and individual rat liver nodules and tumors.

The results of these studies using well characterized and controlled
protocols for hepatocarcinogenesis in inbred rats should provide new
information regarding whether DNA sequence changes occur during the course
of carcinogenesis and if so whether they occur early or late in tumor
development.  Later in the project we will attempt to isolate and
characterize transforming genes from DNA of individual liver tumors.

## Key facts

- **NIH application ID:** 3174299
- **Project number:** 5R01CA036713-06
- **Recipient organization:** DARTMOUTH COLLEGE
- **SAM.gov UEI:** EB8ASJBCFER9
- **Principal Investigator:** JAMES Donald YAGER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $107,166
- **Award type:** 5
- **Project period:** 1983-08-01 → 1990-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3174299

## Citation

> US National Institutes of Health, RePORTER application 3174299, DNA SEQUENCE CHANGES DURING HEPATOCARCINOGENESIS (5R01CA036713-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3174299. Licensed CC0.

---

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