Ad libitum- fed (AL) and food-restricted (FR) Fischer-344 male and female rats were monitored for survival, body weight, and spontaneous neoplasms. Mean and maximal lifespans for each group were inversely related to mean body weights. AL males were the shortest lived (mean lifespan 101 wk) followed by AL females (118 wk), FR males (125 wk), and FR females (132 wk). Gross and microscopic examinations were performed on 851 rats from cross-sectional and longevity components of the study. In FR groups, the incidence of mammary gland fibroadenomas, testicular interstitial cell tumors, and pituitary neoplasms was decreased while the latency of these neoplasms was increased. In longevity components, most FR groups had a higher incidence of leukemia than AL cohorts, but all FR groups had a higher mean age at death for the rats with leukemia. Higher leukemia rate in the FR groups was thought to be a result of their extended mean lifespan.
1. Allaben WT, Chou MW, and Pegram RA (1991). Dietary restriction and toxicological endpoints: An historical overview. In: ILSI Monographs: Biological Effects of Dietary Restriction, L Fishbein (ed). Springer-Verlag, New York, pp. 27–41.
2.
2. Haseman JK, Huff J, and Boorman GA (1984). Use of historical control data in carcinogenicity studies in rodents.Toxicol. Pathol.12(2): 126–135.
3.
3. Haseman JK and Rao GR (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(1): 52–60.
4.
4. Keenan KP (1992). The effect of diet and calorically optimization (calorically restriction) on rat survival and carcinogenicity. Proceeding from the 43rd Annual Meeting of the American College of Veterinary Pathologists, San Diego, CA, November 15–21, p. 227.
5.
5. Lang PL (1991). Changes in life span of research animals leading to questions about validity of toxicologic studies.Chem. Reg. Rep.14:1518–1520.
6.
6. Maeda H, Gleiser CA, Masoro EJ, Murata I, McMahan CA, and Yu BP (1985). Nutritional influences on aging of Fischer 344 rats: II. Pathology.J. Gerontol.40(6): 671–688.
7.
7. Masoro EJ (1992). Retardation of aging processes by food restriction: An experimental tool.Am. J. Clin. Nutr.55: 12505–12525.
8.
8. Moloney WC, Boschetti AE, and King VP (1970). Spontaneous leukemia in Fischer rats.Cancer Res.30: 41–42.
9.
9. Pollard M, Luckert PH, and Synder D (1989). Prevention of prostate cancer and liver tumors in L-W rats by moderate calorically restriction.Cancer64(3): 686–690.
10.
10. Rao GN, Haseman JK, Grumbein S, Crawford DD, and Eustis SL (1990). Growth, body weight, survival and tumor trends in F344/N rats during an eleven-year period.Toxicol. Pathol.18(1): 61–70.
11.
11. Shimokawa I, Yu BP, Higami Y, Ikeda T, and Masoro EJ (1993). Dietary restriction retards onset but not progression of leukemia in male F344 rats.J. Gerontol. Biol. Sci.2(48): B68–73.
12.
12. Stromburg PC (1990). Hemopoietic neoplasms of Fischer 344 rats. In: Atlas of Tumor Pathology of the Fischer Rat, F Stinson Sherman, M Hildegard, and G Reznik Gerd (eds). CRC Press, Boca Raton, Florida, pp. 505–526.
13.
13. Ward JM and Reynolds CW (1983). Large granular lymphocyte leukemia, a heterogenous lymphocytic leukemia in F344 rats.Am. J. Pathol.111: 1–10.
14.
14. Witt WM, Brand CD, Attwood MS, and Soave OA (1989). A nationally supported study on caloric restriction of rodents.Lab. Animal18: 37–43.
15.
1. Ballerini L, Solcia E, Bellini O, Sala L, and Bertazzoli C (1977). Experimental adriamycin cardiomyopathy in the rat.IRCS Med. Sci.5: 431.
16.
2. Barbieri B, Giuliani FC, Bordoni T, et al (1987). Chemical and biological characterization of 4′-iodo-4′-deoxydoxorubicin.Cancer Res.47: 4001–4006.
17.
3. Bristow MR, Sageman WS, Scott RH, Billingham ME, Bowden RE, Kernoff RS, Snidow GH, and Daniels JR (1980). Acute and chronic cardiovascular effects of doxorubicin in the dog: The cardiovascular pharmacology of drug-induced histamine release.J. Cardiovasc. Pharmacol.2: 487–515.
18.
4. Dunn OJ (1964). Multiple comparison using rank sums.Technometries3: 241.
19.
5. Herman EH (1968). Study of the cardiac toxicity of the antibiotic daunomycin in rodents.Fed. Proc.27: 707.
20.
6. Iatropoulos MJ (1984). Anthracycline cardiomyopathy: Predictive value of animal models.Cancer Treat. Symp.3: 3–17.
21.
7. Jaenke RS (1976). Delayed and progressive myocardial lesions after adriamycin administration in the rabbit.Cancer Res.36: 2958–2966.
22.
8. Mettler FP, Young DM, and Ward MJ (1977). Adriamycin-induced cardiotoxicity (cardiomyopathy and congestive heart failure) in rats.Cancer Res.37: 2705–2713.
23.
9. Siegel S (1956). Non Parametric Statistics for the Behavioral Sciences.McGraw-Hill, New York. 184 pp.
24.
10. Solcia E, Ballerini L, Bellini O, Magrini U, Bertazzoli C, Tosana G, Sala L, Balconi F, and Rallo F (1981). Cardiomyopathy of doxorubicin in experimental animals. Factors affecting the severity, distribution and evolution of myocardial lesions.Tumori67: 461–472.
25.
11. Zbinden G, Bachmann E, and Holderegger C (1978). Model systems for cardiotoxic effects of anthracyclines.Antibiot. Chemother.23: 255–270.
