# CHEMICAL TRANSFORMATION NEOPLASTIC PROGESSION & ONCOGENE

> **NIH NIH R01** · WISTAR INSTITUTE · 1987 · $157,531

## Abstract

Cancer is the end result of a multistage, multifactorial process.  The
assays for chemical transformation of Syrian hamster embryo fibroblasts
(HE) and hamster epidermal cells are excellent models in which to study
various factors that may be associated with specific stages in
transformation, from the first morphologic changes induced by a carcinogen
through progression to the neoplastic state.  The objective of this
proposal is to determine whether altered expression or activation of
cellular ras genes plays a role in chemical transformation of hamster
cells, and whether such alterations are associated with any specific stage
during the progression from morphologic to neoplastic transformation.  The
c-ras gene which is most frequently activated in neoplastic transformants
of HE and hamster epidermal cells initiated with benzo(a)pyrene (B(a)P)
will be determined, using DNA transfection into NIH/3T3 cells and
restriction enzyme analysis of transforming activity and of hybridization
patterns with specific ras probes.  The normal hamster homolog of the
activated ras gene will be molecularly cloned, and the coding regions
containing the codons for amino acids 12 and 61 subcloned and sequenced.
The normal gene sequences subcloned into a single-stranded DNA vector will
be used as probes for genomic sequencing of the activated genes in the
neoplastic transformants and of homologous regions in their preneoplastic
progenitors.  It will then be determined when, after treatment of primary
cells with B(a)P and clonal isolation of morphologically altered HE cell
transformants or differentiation-resistant epidermal cell transformants, a
mutation in a ras gene can first be detected by a biochemical test for
restriction polymorphism or genomic sequencing of the DNA.  We will then
determine when, in relation to the progression from morphologic to
neoplastic transformation, that mutated ras gene is expressed, as measured
by its transfectability into 3T3 cells and/or altered production of p21.
These experiments can determine if ras gene activation is or is not a
primary event in chemical transformation of hamster cells.

## Key facts

- **NIH application ID:** 3174944
- **Project number:** 5R01CA037168-03
- **Recipient organization:** WISTAR INSTITUTE
- **SAM.gov UEI:** DW1XZMGNFBL4
- **Principal Investigator:** LEILA DIAMOND
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $157,531
- **Award type:** 5
- **Project period:** 1985-04-01 → 1990-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3174944

## Citation

> US National Institutes of Health, RePORTER application 3174944, CHEMICAL TRANSFORMATION NEOPLASTIC PROGESSION & ONCOGENE (5R01CA037168-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3174944. Licensed CC0.

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