A series of 16 experiments, using a total of 2,000 BD6 rats, was designed in order to assess the ability of 8 individual agents or their combinations to modulate the liver and oesophageal
carcinogenesis induced by multiple doses of
diethylnitrosamine (DEN). Of the
antioxidants tested,
sodium selenite,
ascorbic acid, and
butylated hydroxytoluene generally exhibited protective effects on both types of
tumors. In contrast,
retinoic acid behaved as a promoter of DEN hepatocarcinogenesis, but this effect could be eliminated by its combination with either
selenite or
butylated hydroxytoluene.
Caffeine and
theophylline, when individually assayed, were devoid of significant protective effects, and the latter
methylxanthine stimulated oesophageal
tumorigenesis when administered after exposure to the
carcinogen.
Caffeine tended to decrease the multiplicity of liver
tumors and potentiated the inhibitory effect of
selenite in the liver. Irrespective of combination with
caffeine, treatment with
phenobarbital before each DEN injection tended to reduce the multiplicity of both liver and oesophageal
tumors. On the other hand, the metabolic inhibitor
diethyldithiocarbamate, given after each DEN injection, dramatically enhanced the incidence and multiplicity of oesophageal
tumors. Thus, on the whole, modulation of DEN
carcinogenesis varied depending on test agents, their combinations, dosages, treatment schedules, and target organ.