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Effect of Diet and Animal Care/Housing Protocols on Body Weight, Survival, Tumor Incidences, and Nephropathy Severity of F344 Rats in Chronic Studies
Joseph K. Haseman
Biostatistics Branch, Environmental Diseases and Medicine Program, haseman{at}niehs.nih.gov
Elizabeth Ney
Laboratory of Experimental Pathology, Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA
Abraham Nyska
Laboratory of Experimental Pathology, Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA
Ghanta N. Rao
Laboratory of Experimental Pathology, Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA
Diet is an important environmental factor affecting body weight, survival, and age-related diseases of rodents. The NIH-07 open formula diet was the diet used in the National Toxicology Program's (NTPs) rodent carcinogenicity studies from 1980 to 1994. In 1994 the NTP began using a new diet designated the NTP-2000 diet. This paper compares body weight, survival, tumor incidence, and nephropathy severity in untreated control groups of Fischer 344 (F344) rats fed the NTP-2000 or NIH-07 diets, using data from 22 separate 2-year feed and inhalation studies. The feed studies were conducted in 3 different facilities, and all the inhalation studies were conducted in a single facility. During feed studies, rats were group housed in polycarbonate cages and fed diets in powder (mash) form, while in inhalation studies, rats were housed individually in wire mesh cages, and fed diets in pelleted form. Survival was significantly (p < 0 .05) higher in groups fed NTP-2000 diet compared to the corresponding groups fed NIH-07 diet, irrespective of sex or housing conditions. Use of the NTP-2000 diet was also associated with a decreased incidence of pituitary gland tumors in both sexes and decreased incidences of adrenal pheochromocytoma and preputial gland tumors in males. The incidence and severity of nephropathy was also decreased in animals receiving the NTP-2000 diet, especially males. The decreased nephropathy severity and the decreased incidence of pituitary gland tumors are likely the major factors contributing to the improved survival of rats receiving the NTP-2000 diet relative to those given the NIH-07 diet. These data also support earlier findings that decreased incidences of adrenal pheochromocytoma are associated with reduced nephropathy severity in male F344 rats. Throughout the two-year study female rats receiving the NTP-2000 diet were significantly (p < 0.05) lighter than those receiving the NIH-07 diet. However, it is uncertain if this difference can be attributed to the NTP-2000 diet, since implementation of this diet by the NTP approximately coincided with changes in the F344 rat production colony that resulted in somewhat lighter animals being provided to the NTP. Controls from inhalation studies and feed studies differed significantly (p < 0.01) in the incidence of a variety of tumors, irrespective of diet. This suggests that differences in animal care and housing protocols may impact tumor incidence in F344 rats, most notably pituitary gland and testis tumors.
Key Words: NIH-07 diet • NTP-2000 diet • housing • animal care • body weight • survival • F344 rats • tumor incidence • nephropathy • rodent carcinogenicity studies.
References
- Bieler GS, Williams RL (1993). Ratio estimates, the delta method, and quantal response tests for increased carcinogenicity. Biometrics 49: 793— 801.
- Cheng YS, Moss OR ( 1989). Inhalation exposure systems. In: Concepts in Inhalation Toxicology, McClellan RO, Henderson RF (eds). Hemisphere Publishing, New York, pp 30—33.
- Cotran RS, Kumar V., Robins SL (1994). Cellular injury and cellular death. In: Pathologic Basis of Diseases, 5th ed, Cotran RS, Kumar V, Robins SL (eds). W.B. Saunders Company, Philadelphia, pp 1—35.
- Dinse GE, Haseman JK (1986). Logistic regression analysis of incidental tumor data from animal carcinogenicity experiments. Fundam an Appl Toxicol 6: 44—52.[CrossRef]
- Ettlin RA, Stirnimann P., Prentice DE (1994). Causes of death in rodent toxicity and carcinogenicity studies. Toxicol Pathol 22: 165—178.[Abstract/Free Full Text]
- Haseman JK, Eustis SL, Ward JM ( 1994). Contributing causes of death in rats and the utilization of this information in the statistical evaluation of tumor data. In: ILSI Monograph on the Pathology of Aging Animals, Vol I, Mohr U, Capen C, Dungworth D (eds). ILSI Press, Washington, DC, pp 629—638.
- Haseman JK, Hailey JR, Morris RW (1998). Spontaneous neoplasm incidences in Fischer 344 rats and B6C3F1 mice in two-year carcinogenicity studies: a National Toxicology Program update. Toxicol Pathol 23: 428— 441.
- Haseman JK, Huff JE, Rao GN, Arnold JE, Boorman GA, McConnell EE (1985). Neoplasms observed in untreated and corn oil gavage control groups of F344/N rats and (C57BL/6N x C3H/HeN)F1 (B6C3F1) mice. J Natl Cancer Inst 75: 975—984.[Web of Science][Medline]
[Order article via Infotrieve]
- Haseman JK, Huff JE, Rao GN, Eustis SL (1989). Sources of variability in rodent carcinogenicity studies. Fundam Appl Toxicol 12: 793—804.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Haseman JK, Rao GN (1992). Effects of corn oil, time-related changes and inter-laboratory variability on tumor occurrence in control Fischer 344 (F344/N) rats. Toxicol Pathol 20: 52—60.[Abstract/Free Full Text]
- Haseman JK, Young E., Eustis SL, Hailey JR (1997). Body weight/tumor incidence correlations in long term rodent carcinogenicity studies. Toxicol Pathol 25: 256—263.[Abstract/Free Full Text]
- Knapka JJ, Smith PK, Judge FJ (1974). Effect of open and closed formula rations on the performance of three strains of laboratory mice. Lab Anim Sci 24: 480—487.[Web of Science][Medline]
[Order article via Infotrieve]
- Kurokawa Y., Hayashi Y., Maekawa A., Takahashi M., Kukubo T. (1985). High incidences of pheochromocytomas after long-term administration of Retinol acetate to F344/DuCrj rats. J Natl Cancer Inst 74: 715—723.[Web of Science][Medline]
[Order article via Infotrieve]
- Masoro EJ, Iwasaki K., Gleiser CA, McMahan CA, Seo EJ, Yu BP (1989). Dietary modulation of the progression of nephropathy in aging rats: an evaluation of the importance of protein. Am J Clin Nutr 49: 1217—1227.[Abstract/Free Full Text]
- Miller RG Jr (1966). Simultaneous Statistical Inference. McGraw-Hill, New York.
- National Research Council ( 1985). Guide for the Care and Use of Laboratory Animals. U.S. Govt. Printing Office, Washington, DC NIH Publ 85-23.
- National Research Council ( 1996). Guide for the Care and Use of Laboratory Animals. National Academy Press, Washington, DC.
- National Research Council, Committee on Animal Nutrition (1995). Nutrient requirements of the laboratory mouse. Nutrient Requirements of Laboratory Animals, 4th ed, National Academy of Sciences, Washington, DC pp 80—102.
- National Toxicology Program (NTP) (1992). Specifications for the conduct of studies to evaluate the toxic and carcinogenic potential of chemical, biological and physical agents.
 http://ntserver.niehs.nih.gov/Main_Pages/NTP_CDM_PG.html . - National Toxicology Program (NTP) (1994). Comparative Toxicology Studies of Corn Oil, Safflower Oil, and Tricaprylin in Male F344/N Rats as Vehicles for Gavage. NTP Technical Report 426, NIH Publication No. 94-3157, National Toxicology Program, Research Triangle Park, NC.
- Nyska A., Haseman JK, Hailey JR, Smetana S., Maronpot RR (1999). The association between severe nephropathy and pheochromocytoma in the male F344 rat—the National Toxicology Program experience. Toxicol Pathol 27: 456—462.[Abstract/Free Full Text]
- Nyska A., Hester SD, Cooper RL, Goldman JM, Stocker TE, House D., Wolf DC ( 2002). Single or group housing altered hormonal physiology and affected pituitary and interstitial cell kinetics. Jap J Toxicol Sci 27: 449— 457.
- Nyska A., Leininger JR, Maronpot RR, Haseman JK, Hailey JR (1997). Effect of individual caging versus group caging on the incidence of pituitary tumors in F344 rats: proposed mechanism. Med Hypotheses 50: 525— 529.
- Portier CJ, Bailer AJ (1989). Testing for increased carcinogenicity using a survival-adjusted quantal response test. Fundam Appl Toxicol 12: 731— 737.
- Rao GN (1996). New diet (NTP-2000) for rats in the National Toxicology Program toxicity and carcinogenicity studies. Fundam Appl Toxicol 32: 102—108.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Rao GN (1997). New nonpurified diet (NTP-2000) for rodents in the National Toxicology Program's toxicology and carcinogenesis studies. J Nutr 127: 842S—846S.[Medline]
[Order article via Infotrieve]
- Rao GN (2002). Diet and kidney diseases in rats. Toxicol Pathol 30: 651— 656.
- Rao GN, Crockett PW (2003). Effect of diet and housing on growth, body weight, survival and tumor incidences of B6C3F1 mice in chronic studies. Toxicol Pathol 31: 1—8.[Abstract/Free Full Text]
- Rao GN, Edmondson J., Elwell MR (1993). Influence of dietary protein concentration on severity of nephropathy in Fischer 344 rats. Toxicol Pathol 21: 353—361.[Web of Science][Medline]
[Order article via Infotrieve]
- Rao GN, Edmondson J., Hildebrandt PK, Bruner RH (1996). Influence of dietary protein, fat, and fiber on growth, blood chemistry and tumor incidences in Fischer 344 rats. Nutr Cancer 25: 269—279.[Web of Science][Medline]
[Order article via Infotrieve]
- Rao GN, Haseman JK (1993). Influence of corn oil and diet on body weight, survival, and tumor incidences in F344/N rats. Nutr Cancer 19: 21—30.[Web of Science][Medline]
[Order article via Infotrieve]
- Rao GN, Haseman JK, Grumbein S., Crawford DD, Eustis SL (1990). Growth, body weight, survival, and tumor trends in F344/N rats during an eleven-year period. Toxicol Pathol 18: 61—70.[Web of Science][Medline]
[Order article via Infotrieve]
- Rao GN, Knapka JJ (1987). Contaminant and nutrient concentrations of natural ingredient rat and mouse diet used in chemical toxicology studies. Fundam Appl Toxicol 9: 329—338.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Rao GN, Morris RW, Seely JC (2001). Beneficial effects of NTP-2000 diet on growth, survival, and kidney and heart diseases of Fischer 344 rats in 690 chronic studies. Toxicol Sci 63: 245—255.[Abstract/Free Full Text]
- Rao GN, Piegorsch WW, Haseman JK (1987). Influence of body weight on the incidence of spontaneous tumors in rats and mice of long-term studies. Amer J Clin Nutr 45: 252—260.[Free Full Text]
- Ross MH, Bras G., Ragbeer MS (1970). Influence of protein and caloric intake upon spontaneous tumor incidence of the anterior pituitary gland. J Nutr 100: 177—189.[Abstract/Free Full Text]
- Tarone RE (1975). Tests for trend in life table analyses. Biometrika 62: 679—682.[Abstract/Free Full Text]
- Thigpen JE, Haseman JK, Saunders H., Locklear J., Caviness G., Grant M., Forsythe D. (2002). Dietary factors affecting uterine weights of immature CD-1 mice used in uterotrophic bioassays. Cancer Detect Preven 26: 381— 393.[CrossRef]
- Tischler AS, Powers JF, Pignatello M., Tsokas P., Downing JC, McClain RM (1999). Vitamin D3-induced proliferative lesions in the rat adrenal medulla. Toxicol Sci 51: 9—18.[Abstract/Free Full Text]
- Yoshida M., Ishibashi S., Nakazawa M., Tamura H., Uchimoto H., Kawaguchi K., Yoshikawa K., Hamasu Y., Sumi N. ( 1995). The mechanism of lactitol (NS-4) in inducing adrenomedullary proliferative lesion in rats. J Toxicol Sci 20 (Suppl 1): 37—45.[Medline]
[Order article via Infotrieve]
Toxicologic Pathology, Vol. 31, No. 6,
674-681 (2003)
DOI: 10.1080/01926230390241927
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