POLYAMINE DEPRIVATION STIMULATES NATURAL-KILLER-CELL ACTIVITY IN CANCEROUS MICE

It has recently been established that the total blockade of all endoge nous and exogenous sources of polyamines by a drug containing polyamin e deficient chow (DC-PDC+) could inhibit tumor growth in vivo and incr ease the antitumoral efficacy of chemotherapy drugs. We show here that polyamine deprivation obtained with DC-PDC+ not only influences tumor development via reduction of polyamine concentrations in the tumor it self but, in addition, stimulates cells of the non-specific immune sys tem specialized in tumor cell killing. We report that mice grafted wit h the 3LL carcinoma present a dramatic decrease in the cytotoxic activ ity of their natural killer (NK) cells. When these animals are treated with DC-PDC+, their NK cell activity is completely restored to normal values. Normalization of leucocyte number and differential count was observed as well. With respect to the different components of the DC-P DC+, it was observed that the endogenous and exogenous sources of poly amines have a different degree of impact on tumor development. For exa mple, when only polyamines from digestive sources are deprived, a weak but significant improvement in NK activity and antitumoral effects we re observed, without affecting intratumoral polyamine concentrations. We conclude that polyamines, secreted by the tumor itself as well as a bsorbed through the gastrointestinal tract, could now be considered no t only as autocrine growth factors but also as natural immunosupressiv e factors.