The goal is to continue to develop and employ cultured mammalian cell systems with which to quantify all of the kinds of mutations induced by ionizing radiations, and to illuminate mechanisms of their induction. The rationale is that since mutations underlie genetic diseases including many cancers, in vitro assays can help predicting risks and shed light on processes of carcinogenesis in vivo. The focus will be 137Cs-gamma radiation, as a model agent at various regimens of exposure, e.g. high and low dose rates. Mutation analysis will be carried out in different constructs of AL human-hamster hybrid cells in which a spectrum of mutations from 100,000 to 1.4 x 108 base pairs of DNA can be quantified and resolved by Southern and PCR analysis. The focus will be on chromosomal mutations which appear to be the principal mutation induced by ionizing radiations.
Each specific aim i s designed to characterize the role in mutagenesis (both in terms of the numbers and kinds of mutants induced) of different cellular properties that affect mutagenesis: gene linkage and ploidy, cell cycle phase, DNA repair (of both double strand breaks and base damage), and p53 status (mutant vs wild type). They propose also to clone the MIC1 gene that encodes the S1 antigen which is the principal marker gene employed in the assay so as to be able to study intragenic mutations.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA036447-12
Application #
2871685
Study Section
Radiation Study Section (RAD)
Program Officer
Pelroy, Richard
Project Start
1984-09-01
Project End
2001-01-31
Budget Start
1999-02-01
Budget End
2000-01-31
Support Year
12
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Colorado State University-Fort Collins
Department
Public Health & Prev Medicine
Type
Schools of Veterinary Medicine
DUNS #
112617480
City
Fort Collins
State
CO
Country
United States
Zip Code
80523
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Wilson, A B; Seilly, D; Willers, C et al. (1999) Antigen S1, encoded by the MIC1 gene, is characterized as an epitope of human CD59, enabling measurement of mutagen-induced intragenic deletions in the AL cell system. Somat Cell Mol Genet 25:147-57
Wu, L J; Randers-Pehrson, G; Xu, A et al. (1999) Targeted cytoplasmic irradiation with alpha particles induces mutations in mammalian cells. Proc Natl Acad Sci U S A 96:4959-64
Waldren, C A; Ueno, A M; Schaeffer, B K et al. (1999) Mutant yields and mutational spectra of the heterocyclic amines MeIQ and PhIP at the S1 locus of human-hamster AL cells with activation by chick embryo liver (CELC) co-cultures. Mutat Res 425:29-46

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