INITIATION OF HEPATOCARCINOGENESIS BY ENDOGENOUSLY FORMED N-NITROSOBIS(2-HYDROXYPROPYL)AMINE, N-NITROSODIETHANOLAMINE AND N-NITROSO-2,6-DIMETHYLMORPHOLINE IN RATS

Initiation activities of endogenously formed N-nitrosobis(2-hydroxypro pyl)amine (NBHPA), N-nitrosodiethanolamine (NDELA) and N-nitroso-2,6-d imethylmorpholine (NDMM) were investigated in a modified short-term as say for rat hepatocarcinogenesis. Male Wistar rats were fed 1% bis(2-h ydroxypropyl)amine, 0.5% diethanolamine or 0.25% 2,6-dimethylmorpholin e in the diet plus 0.3% sodium nitrite in the drinking water, Two week s after starting the experimental regimen they underwent 2/3 partial h epatectomy and were then maintained on the respective diets for a furt her week, Following a 2 week recovery period on basal diet the rats we re subjected to a resistant hepatocyte regimen consisting of 0.02% 2-a cetylaminofluorene in the diet for 2 weeks and 1 mg carbon tetrachlori de/kg body wt by gavage at the midpoint. Initiation activity was assay ed by measuring hepatic foci positive for gamma-glutamyltranspeptidase , Numbers of such foci per cm(2) were significantly increased in the g roups given the secondary amines together with nitrite compared with v alues for groups given each precursor or nitrite alone, Further, the n umbers of lesions were essentially similar to those found in rats give n carcinogenic doses of NBHPA, NDELA and NDMM, The results clearly dem onstrate hepatocyte initiation activities of endogenously formed carci nogens, presumably NBHPA, NDELA and NDMM.