Oil gavage effects on tumor incidence in the National Toxicology Program's 2-year carcinogenesis bioassay

Numerous studies have reported a positive relationship between dietary fat and chemically induced tumor incidence. The results of the 2-year carcinogenesis bioassay used by the National Toxicology Program (NTP), in which test compounds were administered to rodents by corn oil gavage, provide an opportunity to compare the effects of fat on chemically induced and naturally occurring tumors. Oil gavage increases the fat intake about threefold, equivalent to a 15% fat diet. Only 2 oil gavage effects were observed in the NTP carcinogenesis bioassay. First, pancreatic hyperplasia was increased from 2.6% in untreated controls to 12.6% in male Fischer 344/N vehicle control rats; however, this sporadic and weak effect did not influence the outcome of carcinogenesis bioassays. Second, leukemia/lymphoma incidence was about 50% lower in male vehicle controls than in the untreated control rats; in contrast, this strong effect increased survival by 8-10%. Therefore, oil gavage had an apparent protective effect in male Fischer 344/N rats. The absence of growth enhancement for the relatively high background level of tumors in oil gavage-treated rats was remarkable and is inconsistent with observations in rat mammary tumor model studies. Because it is impossible to extrapolate the enhancing effect of a high fat diet on tumor growth from rodent tumor models to the NTP carcinogenesis bioassay, great caution should be used in extrapolating from rodent tumor model studies to the human situation.