Carcinogenesis, Vol. 21, No. 11, 1959-1964,
November 2000
© 2000 Oxford University Press
Molecular Epidemiology and Cancer Prevention |
Effects of calorie restriction on thymocyte growth, death and maturation
1 Department of Carcinogenesis, The University of Texas–M.D.Anderson Cancer Center, Smithville, TX 78957,
2 Basic Research Laboratory, NCI–FCRDC, Frederick, MD 21702-1201,
3 Phytonutrients Laboratory, BHNRC, ARS, USDA, Beltsville, MD 20705 and
4 Division of Cancer Prevention, NCI, Bethesda, MD 20892-7105, USA
We previously reported that calorie restriction (CR) significantly delays the spontaneous development of thymic lymphomas and other neoplasms in p53-deficient mice and their wild-type littermates. The purpose of the present study was to further characterize the anti-lymphoma effects of CR by assessing thymocyte growth, death and maturation in response to acute (6 day) and chronic (28 day) CR regimens. Male C57BL/6J mice fed a CR diet (restricted to 60% of control ad libitum intake) for 6 days displayed a severe reduction in thymic size and cellularity, as well as a decrease in splenic size and cellularity; these declines were sustained through 28 days of CR. Mice maintained on a CR diet for 28 days also displayed a significant depletion in the cell numbers of all four major thymocyte subsets defined by CD4 and CD8 expression. Analysis within the immature CD4–8– thymocyte subset further revealed an alteration in normal CD44 and CD25 subset distribution. In particular, CR for 28 days resulted in a significant decrease in the percentage of the proliferative CD44–25– subset. In addition, a significant increase in the percentage of the early, pro-T cell CD44+25– population was detected, indicative of a CR-induced delay in thymocyte maturation. Taken together, these findings suggest that CR suppresses (through several putative mechanisms) lymphomagenesis by reducing the pool of immature thymocytes that constitute the lymphoma-susceptible subpopulation.
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