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

Abstract

The tumor initiating activities of nitrosomethylbenzylamine (NMBzA), an esophageal carcinogen, and nitrosodimethylamine (NDMA), a hepatocarcinogen, were compared in rat liver using modifications of the initiation assays of Tsuda et al. (Cancer Res., 40, 1157, 1980) and Pitot et al. (Nature, 271, 456, 1978). Equimolar doses of NMBzA or NDMA (33.5 mu-mol/kg) were injected i.p. into male Sprague-Dawley rats 18 h after partial hepatectomy. Following selection, foci of preneoplastic hepatocytes were detected by histochemical staining for gamma-glutamyltranspeptidase. Nitrosomethylamylamine (NMAmA), 115 mumol/kg), also an esophageal carcinogen, was tested in the assay of Tsuda et al., and nitrosodiethylamine (NDEA, 33.5 mumol/kg), a hepatic and esophageal carcinogen, was tested in the assay of Pitot et al. Both NDMA and NDEA induced significant increases in the number 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 metabolize both 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 wave of DNA synthesis in vivo in the regenerating liver. The results demonstrate that in contrast to NDMA and NDEA, NMBzA and NMAmA lack tumor initiating activity in the liver.