Mechanisms potentially responsible for formation, activation, and detoxication of carcinogenic N-nitroso compounds in the human body are under intense investigation. Evidence implicating the alpha-nitrosamino radical as the critical intermediate in both activation and inactivation of the potent carcinogen, N-nitrosodimethylamine, has been obtained through deuterium isotope effect studies. Certain iron species have been found to convert amines to their carcinogenic N-nitroso derivatives in nonacidic media modeling those potentially found in vivo or in the environment; the rate law is zero order in nitrite, suggesting that the reaction may be as fast in the limit of very low nitrite concentrations (such as those found in the body or in the environment) as it is under the laboratory conditions used. The deuterium isotope effect on the carcinogenicity of 1,2-dimethylhydrazine suggests that at least three different mechanisms of tumor induction are simultaneously operative in dimethylhydrazine-treated mice. Urine specimens from a region of China having a very high incidence of esophageal cancer are being analyzed in a search for correlations with the degree of progression toward malignancy in the individual donors. The chemistry of a powerful mutagen isolated from human feces is being investigated with the aim of developing means of verifying its integrity, as well as stabilizing and solubilizing it during studies of its biological properties in mammals. The first O- trimethylsilylated nitrosamine salts have been prepared. Nitrite ion has been found to react with the common solvent, methylene chloride, to generate a powerful nitrosamine-forming intermediate.

Agency
National Institute of Health (NIH)
Institute
Division of Cancer Epidemiology And Genetics (NCI)
Type
Intramural Research (Z01)
Project #
1Z01CP004542-16
Application #
3939615
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
16
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Cancer Epidemiology and Genetics
Department
Type
DUNS #
City
State
Country
United States
Zip Code