Published in Cancer Detection and Prevention 2000; 24(Supplement 1).

The mechanism of the age - related reduced tumor progression rate in AKR lymphoma involves a modification in apoptotic cell death - related molecules

J Leibovici DSc, O Itzhaki MSc, E Skutelsky PhD, J Sinai PhD, A Siegal MD, M Michowitz MD, T Kaptzan MSc

Dept Pathology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel,

Numerous studies have been dedicated to the aging- carcinogenesis relation, but only few dealt with the host age effect on tumor progression. Certain cancers evolve at a slower rate in aged as compared to young patients. The mechanism of this less aggressive behavior in the aged is, however, not yet clear. Reduced cell proliferative capacity has been proposed. We suggest an increased programmed cell death rate in tumors growing in old as compared to young individuals. AIMS: The present study tested the above hypothesis, by examining the extent of apoptosis in AKR lymphomas from young and old mice. METHODS: Apoptosis was tested by cell morphology, DNA flow cytometry and DNA fragmentation in agarose gel electrophoresis. Expression of Bcl-2 and Fas proteins was evaluated by FACS analysis using fluorescent antibodies. RESULTS: Increased apoptosis in tumors from old as compared to young animals was observed by cell morphology, sub G1 cell population percentage and DNA fragmentation, in four AKR lymphoma variants. Old mice lymphoma cells showed a lower Bcl-2 protein expression than those from young animals. The Fas antigen, on the contrary, displayed higher expression levels on old mice-derived lymphoma cells. CONCLUSIONS: Our results, at both cellular and molecular level, indicate that increased apoptotic cell death in tumors from old as compared to those from young animals constitutes one of the mechanisms of the age- related reduced tumor progression rate in the aged. This phenomenon might have theoretical as well as therapeutic implications, since radiotherapy and numerous chemotherapeutic and immunotherapeutic agents are known to act via induction of apoptosis. Age - adapted cancer therapy might be a necessity.

KEY WORDS: Tumor progression, Aging, Apoptosis, AKR lymphoma.

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Paper presented at the International Symposium on Impact of Biotechnology on Cancer Diagnostic & Prognostic Indicators; Geneva, Switzerland; October 28 - 31, 2000; in the section on cell cycle inhibitors.