Patterns of tumor incidence in two-year cancer bioassay feeding studies in Fischer 344 rats.
Patterns of tumor incidence in 25 of the National Toxicology Program's (NTP's) two-year cancer bioassay feeding studies in Fischer 344 rats were investigated. It was found that the overall frequencies of statistically significant (P less than 0.01) increases and decreases in organ-specific tumor incidence in treated groups relative to controls were approximately the same. The decreases were due primarily to mammary gland fibroadenomas in females (which were clearly associated with decreased weight gain in the treated groups) and leukemia/lymphoma in both sexes (which were frequently associated with increased liver tumor incidences in the treated groups). A clear explanation for this latter association was not apparent. The increased tumor incidences in the treated groups relative to controls were due primarily to liver neoplastic nodules. Treated animals of either sex had slightly (but significantly) improved overall survival relative to controls. The intra- and inter-laboratory variability in control tumor incidence frequently exceeded what one would expect to find by chance alone. This investigation helps explain the decreased tumor incidences observed in many NTP feeding studies. It also indicates that attention should be directed toward the determination of underlying mechanisms responsible for the negative correlation between the incidences of liver tumors and leukemia/lymphoma.
D000818:Animals; D001681:Biological Assay; D005260:Female; D007942:Leukemia, Experimental / Q000139:chemically induced; D008113:Liver Neoplasms / Q000139:chemically induced; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced; D009374:Neoplasms, Experimental / Q000139:chemically induced*; D051381:Rats; D011916:Rats, Inbred F344; D012737:Sex Factors