ANALYSIS OF NATIONAL TOXICOLOGY PROGRAM RODENT BIOASSAY DATA FOR ANTICARCINOGENIC EFFECTS

We reanalyzed data from 218 two-year rodent carcinogenicity studies ca rried out by the National Toxicology Program (NTP). These data were or iginally collected for the purpose of identifying potential human carc inogens. However, the objective of our analysis was to investigate the frequency of possible anticarcinogenic effects in these data, since r ecurring cases of chemical-associated tumor reductions have been noted in the course of these studies over time. Our analysis reveals that m ost (> 90%) NTP-tested chemicals show at least one statistically signi ficant (p < 0.05) decrease in site-specific tumor incidence. Because o f the large number of statistical comparisons made in a long-term bioa ssay, random variability can account for many of these tumor decreases . However, we found that certain tumors (predominantly those with a hi gh spontaneous incidence) show chemically related decreases far more f requently than chance expectation. Many of these decreases, particular ly those for pituitary and mammary gland tumors, adrenal pheochromocyt oma and uterine polyps in rats and liver and lung tumors in mice, are associated with the reduced body weights frequently observed in the do sed groups. The chemically related decreased incidences of leukemia in rats appear to be related to spleen damage, i.e., chemically related splenic toxicity is evident for most chemicals showing decreased incid ences of leukemia. While random variability, associations with body we ight and splenic toxicity can account for most of the decreased tumor incidences observed in NTP studies, there are other tumor decreases th at could not be totally explained by these factors. Further investigat ions of possible mechanisms of action are underway. These data are rel evant to the concept of chemoprevention as well as to the task of usin g long-term laboratory animal studies to predict enhanced human enviro nmental-cancer risk for regulatory purposes.