Comparative tumor initiating activities of N-nitrosomethylbenzylamine and N-nitrosodimethylamine in rat liver

The tumor initiating activities of nitrosomethylbenzylamine(NMBzA), an esophageal carcinogen, and nitrosodimethylamine(NDMA), a hepatocarcinogen, were compared in rat liver usingmodifications of the initiation assays of Tsuda et al. (CancerRes., 40, 1157, 1980) and Pitot et al. (Nature, 271, 456, 1978).Equimolar doses of NMBzA or NDMA (33.5 µmol/kg) were injectedi.p. into male Sprague-Dawley rats 18 h after partial hepatectomy.Following selection, foci of preneoplastic hepatocytes weredetected by histochemical staining for / glutamyltranspeptidase.Nitrosomethylamylamine (NMAmA), 115 µmol/kg), also anesophageal carcinogen, was tested in the assay of Tsuda et al.,and nitrosodiethylamine (NDEA, 33.5 µmol/kg), a hepaticand esophageal carcinogen, was tested in the assay of Pitotet al. Both NDMA and NDEA induced significant increases in thenumber of preneoplastic foci above background. In contrast,neither NMBzA nor NMAmA increased the number of foci above background.Microsomes from regenerating liver had a lower capacity to metabolizeboth NDMA and NMBzA compared to microsomes from intact liver,but the decrease in activity was similar for both compounds.Neither NDMA nor NMBzA significantly inhibited the first waveof DNA synthesis in vivo in the regenerating liver. The resultsdemonstrate that in contrast to NDMA and NDEA, NMBzA and NMAmAlack tumor initiating activity in the liver.