Suppression of adenocarcinoma by the immunological consequences of calorie restriction

Abstract

EARLIER extensive studies have indicated that calorie restriction as well as protein and amino acid restriction inhibit the spontaneous development of mammary or lung adenocarcinomas, hepatomas and certain chemical carcinogen-induced tumours in rodents^1–4. Jose and Good^5–7 and Cooper et al.⁸ have shown that chronic moderate protein deprivation in mice and rats dramatically depresses antibody production while increasing, or permitting maintenance of, vigorous cell-mediated immune responses. The latter include abilities to resist virus infection, reject skin allografts and develop killer-cell activity against syngeneic and allogeneic tumour cells. More profound chronic protein deprivation, however, depresses both cell-mediated and humoral immunity^7,9. Walford et al.^10,11 have shown that calorie restriction delays development of immune functions at an early age but prolongs maintenance of immunological capacity and survival in long lived, tumour-free mice. Further, Fernandes et al.¹² have shown that dramatic prolongation of life of autoimmunity-prone, short lived mice was produced by life-long calorie restriction, and that tumours did not appear in these mice. Although some of the findings clearly link moderate protein and calorie restriction to heightened cellular immunity, no definitive efforts have yet been made to compare directly the influence of dietary restriction on spontaneous tumour development and immunological functions. This report presents observations on the influence of calorie restriction on development of spontaneous mammary adenocarcinoma in mice and relates the suppression of tumour development observed to alterations in immune functions produced by calorie restriction at weaning.