Effects of Diethylstilbestrol and Estramustine Phosphate (Estracyt) on Natural Killer Cell Activity and Tumor Susceptibility in Male Mice

Abstract

The effects of estramustine phosphate (EMP) and diethylstilbestrol (DES) on natural killer (NK) cell activity, tumor growth, and artificial metastases were investigated in male C57BL/6 mice. Kinetic analysis and studies at the single-cell level indicated that EMP did not influence the number of NK cells but interfered with their lytic activity thereby reducing the actual killer capacity. NK cells from EMP-exposed animals responded normally to the interferon inducer Poly I:C which restored NK activity to control levels. Spleen cells from DES-treated animals had lytic activity comparable to that of control animals. However, more detailed analysis showed that DES reduced the number of lymphocytes able to recognize target cells, while the individual NK cell had an increased lytic activity and recycling capacity. Moreover, NK cells from DES-treated animals were refractory to poly-I:C stimulation, suggesting that they were prestimulated in vivo. The pertubations of the NK cell system induced by both EMP and DES were reversible and normalization of NK activity was reached within a week. The incidence of tumor takes after subcutaneous inoculation of the syngeneic Lewis lung carcinoma was increased in EMP as well as DES-treated animals. Artificial lung metastasis produced by intravenous injection of the same tumor was increased in EMP but not in DES-exposed animals.