# ERROR PRONE DNA SYNTHESIS AND ONCOGENE MUTAGENESIS

> **NIH NIH R01** · UNIVERSITY OF CHICAGO · 1989 · $172,088

## Abstract

Activation of the c-Ha-ras oncogene can occur by point mutation at a
limited number of sites.  c-Ha-ras-containing plasmids treated with
chemical carcinogens yield transformants on introduction into recipient
human cells.  These observations suggest the following questions:  a) Are
the mutations the result of mispairing at a targeted site or does
carcinogen treatment induce an error-prone condition in the cells?; b) Are
segments of the c-Ha-ras oncogene particularly susceptible to mutation
because of their sequence or does selection alone account for the frequency
of change to a transformed state.  We plan to study these questions
utilizing an in vitro DNA system obtained from human cells and with
plasmids containing c-Ha-ras.  We propose:  1) to replicate such plasmids
in single and double stranded form in vitro using purified prokaryotic and
eukaryotic enzymes; 2) to develop mammalian cell extracts and partially
purified systems which will replicate c-Ha-ras; 3) to apply previously
developed methodology to the replication of carcinogen-reacted c-Ha-ras
templates; 4) to utilize extracts prepared from carcinogen-reacted cells to
see whether they promote adduct bypass more readily, as would be expected
if an inducible system had developed; 5) to assay the reaction products for
mutation by transfection of rodent cells to the transformed state; and 6)
to study the role of deoxynucleoside triphosphate pool bias, as affected by
treatment with carcinogen, to see whether it is possible to account for
increases in mutability on the basis of pool effects.  These in vitro
studies should suggest answers to the questions asked and should also
provide information useful in the design of plasmids for in vivo tests of
mutability.  The long term goal of these studies is the determination of
how nucleotide sequence and the physiological state of the cell interact in
the production of precarcinogenic mutagenic events.

## Key facts

- **NIH application ID:** 3170362
- **Project number:** 5R01CA032436-08
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **SAM.gov UEI:** ZUE9HKT2CLC9
- **Principal Investigator:** BERNARD S. STRAUSS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $172,088
- **Award type:** 5
- **Project period:** 1982-05-01 → 1990-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3170362

## Citation

> US National Institutes of Health, RePORTER application 3170362, ERROR PRONE DNA SYNTHESIS AND ONCOGENE MUTAGENESIS (5R01CA032436-08). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3170362. Licensed CC0.

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