Modulation of natural killer cell functional activity in athymic mice by beta-carotene, oestrone and their association.

In athymic mice, Natural Killer (NK) cells influence the take rate and growth of human malignant tissue xenografts. To confirm preliminary results, comparative experiments were conducted to study the effects of beta-carotene, oestrone and their association on the cytolysis mediated by spleen NK cells from athymic mice receiving these different treatments. Target cells consisted of YAC-1 malignant cells. With a 65% increase of cytolysis (ratio effector/target 50:1), beta-carotene induced a significant activation of NK cells (p < 0.002). This effect could be attributed to its antioxidant properties and confirmed by a moderate increase in erythrocyte glutathione peroxidase activity. On the contrary, oestrone resulted in a significant decrease of cytolysis (p < 0.001). In this case, the prooxidant properties of oestrone could explain its effect on NK cells and agree with the increase of intracellular reduced glutathione level observed. When mice received the combination beta-carotene-oestrone, their opposite effects on NK cell activity were counterbalanced, leading to a moderate change of cytolysis.

Effect of oestrone on the natural killer (NK) cell activity, antioxidant status and tumour growth in athymic mice xenografted with human tumours.

Natural killer (NK) cells have been described as being very sensitive to oxidative stress. Thus it has been previously shown that chronic administration of oestrone in drinking water of athymic mice xenografted with a wide variety of human tumours, increases their growth and development. In this study an investigation was made to see whether oestrone supplementation could influence the NK cell activity by changes in the antioxidant defences which result in an oxidative stress and influence the proliferation of tumours. Supplementary oestrone was administered in drinking water of athymic mice xenografted with two different human tumours which lack oestrogen receptors: a bladder carcinoma and a small-cell lung carcinoma. The growth of the urothelial carcinoma was poorly affected by oestrone, but oestrone significantly (p<0.01) increased the proliferation of the small-cell lung carcinoma. The average uterus weight was increased by 62% in oestrone treated mice with no modifications in plasma zinc and selenium status, nor in erythrocyte copper zinc superoxide dismutase level. Nevertheless a slight decrease in erythrocyte glutathione peroxidase activity was noted. Trace elements and antioxidant enzymes in liver homogenates remained unchanged. Oestrone treatment also had no effect on plasma and liver lipid peroxides. The immune response was evaluated by measuring NK activity of splenocytes against 51Cr labelled YAC-I target cells. A 35.5% decrease in the NK activity (p<0.001) was observed after oestrone treatment and may be responsible for graft tolerance. However, the results of these experiments seem to exclude the role of oxidative stress in the modulation of NK activity.