We plan to study the chemistry and biochemistry of the reaction between nitrite and creatinine (CRN), since nitrosation-denitrosation of CRN produced methylurea (MU), presumably via formation of the carcinogen methylnitrosourea (MNU). This follows our discovery that nitrosation-denitrosation of dried fish and fried bacon produces MU, arising in part (at least in the fish) from CRN, of which 3-4 g./kg. occurs in these foods. Since CRN is an important food constituent and nitrosourea formation in the stomach may be involved in the etiology of gastric and other types of cancer, we shall determine (a) the route whereby CRN yields MU and, presumably, MNU [to establish whether CRN-5-oxime, 1-methylhydantoin-5-oxime (MHO) and related compounds are intermediates] and the rates of the reactions involved, (b) whether the probable intermediates CRN-5-oxime and MHO occur in high-CRN foods, (c) whether CRN and nitrite react in the rodent stomach to give CRN oxime, MHO, MNU, and MU, as detected by analysis of urine and gastric contents, and (d) whether administration to humans of foods rich in CRN and nitrate will lead to urinary excretion of CRN oxime and MHO, and whether vitamin C can prevent this. These studies are designed to explore the significance of in vivo CRN nitrosation and offer means of detecting this by urine analysis and of inhibiting the process.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA030593-03
Application #
3169310
Study Section
Chemical Pathology Study Section (CPA)
Project Start
1983-02-01
Project End
1987-01-31
Budget Start
1985-02-01
Budget End
1987-01-31
Support Year
3
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Nebraska Medical Center
Department
Type
Overall Medical
DUNS #
City
Omaha
State
NE
Country
United States
Zip Code
68198