Modifying effects of a mixture of acetaminophen, aspirin, dipyrone and ethenzamide on a multiorgan initiation model and its carcinogenicity in male F344 rats

Six-week-old male F344 rats were given a mixture of 0.01% diethylnitrosamine, 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine and 0.02% N-methyl-N′-nitro-N-nitrosoguanidine in their drinking water for 1 week. When 0.8%, 0.4%, or 0% of a mixture of non-steroidal anti-inflammatory drugs (NSAIDs) (acetaminophen, aspirin, dipyrone plus ethenzamide) was given after treatment with initiators in their food from weeks 2 to 68, the incidences of liver cell tumors in the rats were 68% (P<0.001), 25% and 8%, respectively, but those of other tumors were not different. Administration of NSAIDs from weeks 2 to 104 without initiators showed no carcinogenicity. From the results of medium-term liver bioassay, it was suggested that dipyrone and ethenzamide had promoting effects and acetaminophen had an inhibitory effect on rat hepatocarcinogenesis.