This proposal deals with the use of ESR in spin-labelling and spin trapping studies of possible free radicals involved in the initiation and/or promotion phase of carcinogenesis. Studies are directed to free radicals produced in the decomposition of the nitroroamine and amides. Mutagenesis assays are developed to study the effects of these free radicals in the Ames tester system. Spin-labelling, reconstitution, melting and digestion studies have been designed to probe the interaction between activated carcinogens and active and inactive chromatin at nucleosomal level. Studies on the role of the HMG proteins in defining active chromatin are described. Spin-labelling and spin-trapping studies have also been designed to probe the effect of structural conformational changes on reconstituted cytochrome P-450 mixed function oxidase substrate specificity.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA042013-03
Application #
3182743
Study Section
Chemical Pathology Study Section (CPA)
Project Start
1985-07-01
Project End
1989-05-31
Budget Start
1987-06-01
Budget End
1988-05-31
Support Year
3
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Utah State University
Department
Type
Schools of Arts and Sciences
DUNS #
City
Logan
State
UT
Country
United States
Zip Code
84322
Keller, R J; Rush, J D; Grover, T A (1991) Spectrophotometric and ESR evidence for vanadium(IV) deferoxamine complexes. J Inorg Biochem 41:269-76
Keller, R J; Coulombe, R A; Sharma, R P et al. (1989) Oxidation of NADH by vanadium compounds in the presence of thiols. Arch Biochem Biophys 271:40-8
Keller, R J; Coulombe Jr, R A; Sharma, R P et al. (1989) Importance of hydroxyl radical in the vanadium-stimulated oxidation of NADH. Free Radic Biol Med 6:15-22
Keller, R J; Sharma, R P; Grover, T A et al. (1988) Vanadium and lipid peroxidation: evidence for involvement of vanadyl and hydroxyl radical. Arch Biochem Biophys 265:524-33
Grover, T A; Ramseyer, J A; Piette, L H (1987) Photolysis of nitrosamines and nitrosamides at neutral pH: a spin-trap study. Free Radic Biol Med 3:27-32