We intend to quantify, characterize and compare the spectrum of mutations produced by ionizing radiations in human x hamster hybrid AL cells and in mouse lymphoblastoid L5178Y tk+/- cells using quantitation of loss of phenotype and molecular and cytogenetic analyses. We will focus on multilocus, chromosomal mutations. Later we intend to extend these analyses to a new hybrid construct (XR1/11) which is deficient in repair of double strand breaks but which, like AL, contains human chromosome 11. We also propose to characterize mutation in a line of human fibroblasts (EJ30) made heterozous at the thymidine kinase (tk) and/or S1 antigen locus. Our goals are to determine: (1) if different kinds, or different proportions, of particular mutations are produced at different loci; (2) how human and rodent cell lines may differ in this regard; (3) if ionizing radiations produce a particular and specific spectrum of mutations; and (4) the role of repair in mutagenesis. Mutations induced by X-ray, gamma rays and neutrons will be quantified by selection for the homogzyous tk-/- phenotype in mouse L5178Y and human EJ30 cells and for loss from AL and XR1/11 cells of the surface antigens (S1,S2,S3) coded by the human chromosome 11. Mutation in hypoxanthine guanine phosphoribosyltransferase (hprt) will provide a quantitative benchmark; UV and/or ethylmethane sulfonate (EMS) will serve as comparison mutagens. We will seek signature mutations unique to radiation characterized by DNA probes and other recombinant techniques.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA056392-01
Application #
3200772
Study Section
Special Emphasis Panel (SRC (40))
Project Start
1992-04-03
Project End
1996-03-31
Budget Start
1992-04-03
Budget End
1993-03-31
Support Year
1
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Colorado State University-Fort Collins
Department
Type
Schools of Veterinary Medicine
DUNS #
112617480
City
Fort Collins
State
CO
Country
United States
Zip Code
80523
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