New methodologies are proposed utilizing a) hybrid Chinese hamster ovary cells containing particular human chromosomes providing human cell surface antigenic markers; b) selection methods for isolating specific mutants which have lost particular markers; c) recombinant DNA techniques for identifying specific, mapped human DNA sequences that may be lost as a result of mutation; and d) a combination of these various methodologies to detect and quantitate the frequency of translocations. These various operations will be combined in a single procedure which promises to analyze the results of exposure of these cells to physical, chemical and biological agents in terms of each of the principal mutagenic actions known to be important in human diseases: localized mutations, small deletions, large deletions, chromosome loss and translocations. In addition, this approach promises to yield quantitative measurement of the dose response of each mutagen for each type of lesion with a sensitivity many times greater than previously achieved. It is also proposed to apply these methodologies for detection of situations representing human health hazards and for study of aspects of the mutagenic process.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES003746-03
Application #
3251374
Study Section
Mammalian Genetics Study Section (MGN)
Project Start
1985-06-15
Project End
1988-05-31
Budget Start
1987-06-01
Budget End
1988-05-31
Support Year
3
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Eleanor Roosevelt Institute for Cancer Research
Department
Type
DUNS #
City
Denver
State
CO
Country
United States
Zip Code
80206
Collins, A R; Black, D T; Waldren, C A (1988) Aberrant DNA repair and enhanced mutagenesis following mutagen treatment of Chinese hamster Ade-C cells in a state of purine deprivation. Mutat Res 193:145-55
Puck, T T (1987) Genetic regulation of growth control: role of cyclic AMP and cell cytoskeleton. Somat Cell Mol Genet 13:451-7
Waldren, C; Correll, L; Sognier, M A et al. (1986) Measurement of low levels of x-ray mutagenesis in relation to human disease. Proc Natl Acad Sci U S A 83:4839-43