This project will focus on three areas related to nitrosamine carcinogenesis: (1) development of analytical methods for N-nitrosamines, especially methods suitable for rapid, accurate and large scale screening; (2) chemical studies designed to elucidate the reaction pathway and reaction conditions for the destruction of N-nitrosamines by ascorbic acid; and (3) in vivo studies using the swine as the experimental animal. The analytical studies will utilize the formation of nitrosyl chloride, from the reaction between anhydrous hydrogen chloride gas and an anhydrous solution of N-nitrosoamines, as the basis of a simple and rapid screening method. Three approaches will be examined: (1) reaction with solid potassium iodide to form free iodine; (2) addition of NOC1 to tetramethylethylene to form a blue product; and (3) addition of NOC1 to a film on a quartz crystal. The latter utilizes a piezoelectric effect that has a sensitivity of 10 to the -12 grams. Initial work will focus on human blood. The in situ capability of the differential pulse polarographic technique will be used to study the reaction between ascorbic acid and preformed nitrosamines. The kinetics, products and reaction conditions will be established. Since it is known that ascorbic acid can, in some instances, prevent the formation of nitrosamines, it is equally important to know under what conditions ascorbic acid can destroy nitrosamines. Through the use of special surgical procedures extensive metabolic and biological studies will be conducted using the swine. This animal has been selected because its physiology and antomy more closely resembles that of the human than does the physiology of the usual laboratory animal. Initial experiments will monitor portal and hepatic blood following oral dosing in order to study absorption and the role of the liver in nitrosamine metabolism.
| Thurmon, J C; Nelson, D R; Bevill, R F et al. (1987) Surgical procedure for chronic biliary sample collection in pigs. Am J Vet Res 48:988-9 |
| Harrington, G W; Magee, P N; Pylypiw Jr, H M et al. (1987) The pig as an animal model for the study of nitrosamine metabolism. IARC Sci Publ :132-4 |
| Gombar, C T; Pylypiw Jr, H M; Harrington, G W (1987) Pharmacokinetics of N-nitrosodimethylamine in beagles. Cancer Res 47:343-7 |
| Anderson, L M; Harrington, G W; Pylypiw Jr, H M et al. (1986) Tissue levels and biological effects of N-nitrosodimethylamine in mice during chronic low or high dose exposure with or without ethanol. Drug Metab Dispos 14:733-9 |
| Harrington, G W; Eshraghi, J; Pylypiw Jr, H M et al. (1986) Formation of an N-nitrosamine by oxidation. Cancer Lett 32:187-91 |
| Pylypiw Jr, H M; Zimmerman, F; Harrington, G W et al. (1985) Apparatus for trace determination of volatile N-Nitrosamines in small samples. Anal Chem 57:2996-7 |
