[Antitumor mechanisms of carboxyethyl-germanium sesquioxide (Ge-132) in mice bearing Ehrlich ascites tumors].
The administration of IFN-containing sera (Ge-sera) obtained from Ge-132-treated mice (Ge-mice) or the passive transfer of macrophages (M phi) to mice bearing ascites tumors resulted in the inhibition of tumor growth. The cooperative role of Ge-sera and Ge-M phi in the display of Ge-132-antitumor activity was studied. When mice were pretreated with antimouse IFN gamma antiserum, no IFN-inducing or antitumor activities of the compound were detected. Cytotoxic activities were detected in peritoneal M phi of mice treated with Ge-sera, and passive transfer of these M phi to tumor-bearing mice resulted in the inhibition of tumor growth. When tumor-bearing mice were pretreated with substances toxic to M phi, no antitumor activity of Ge-sera was observed. However, Ge-132 antitumor activity was observed in mice depleted of T-cells, even though the antitumor effects of the compound itself were not demonstrable in T-cell-depleted mice. Therefore, a part of the antitumor activity of Ge-132 appears to be expressed as follows: Ge-132 stimulates T-cells to produce circulating lymphokine(s) which are inactivated by anti-IFN gamma treatment; activated M phi are generated from resting M phi by these lymphokine(s); the transplanted tumors are inhibited by these M phi.