Initiation activity of endogenously synthesized N-nitrosobis(2-hydroxypropyl)amine in the rat liver

The initiation potential of N-nitrosobis(2-hydroxypropyl)amine (NDHPA) endogenously synthesized from bis(2-hydroxypropyl)amine (DHPA) or tris(2-hydroxypropyl)amine (THPA) in the presence of sodium nitrite (NaNO2) was investigated in the rat liver by quantitation of hepatocellular foci showing phenotypic expression of glutathione S-transferase placental form (GST-P). The investigation consisted of two experiments. In the first, male Wistar rats were divided into six groups as follows: group 1 was non-treated; groups 2 and 3 received 0.15% and 0.3% NaNO2, respectively; group 4 received 1% DHPA; groups 5 and 6 received 1% DHPA together with 0.15% and 0.3% NaNO2, respectively. In experiment 2, the same protocol was used except that 2% THPA was substituted for 1% DHPA. The treatments were continuous until sacrifice at week 94 in experiment 1 and week 104 in experiment 2. As a result putative preneoplastic GST-P-positive foci observed in the liver and increased dose-dependently in rats from groups 5 and 6 which had received DHPA and NaNO2, but not in rats administered THPA and NaNO2. The results indicate that endogenously synthesized NDHPA from DHPA and NaNO2 is capable of initiating neoplastic development in the rat liver.