THE PROTECTIVE ROLE OF AMMONIUM TRICHLORO(DIOXOETHYLENE-O,O')TELLURATE IN COMBINATION WITH SEVERAL CYTOTOXIC DRUGS ACTING BY DIFFERENT MECHANISMS OF ACTION

We have demonstrated previously that the immunomodulator AS101 can pro tect mice from acute lethal toxicity mediated by high doses of radiati on or chemotherapy. The compound was shown to rescue mice from toxic e ffects of cyclophosphamide or 5-fluorouracil. The results presented he rein demonstrate that pretreatment of mice with AS101 protects them fr om lethal effects of several chemotherapeutic drugs acting by distinct mechanisms. At sublethal doses, AS101 could prevent hemopoietic damag e caused by the drugs. A significantly higher proportion of colony for ming cells granulocyte-macrophage as well as a higher level of colony stimulating factor secretion by bone marrow (BM) cells was observed in mice pretreated with AS101 before injection of doxorubicin or cyclohe xylchloroethylnitrosourea. Moreover, a significantly higher rate of su rvival was observed in mice injected with AS101 before treatment with lethal doses of these drugs. AS101 could also rescue BM stromal cells from damages caused by doxorubicin. We show that injection of mice wit h AS101 or pretreatment of BM cells with AS101 protects BM-colony form ing cells granulocyte-macrophage from toxic effects of etoposide. We s uggest that the protective effects of AS101 against damages caused by a variety of cytotoxic drugs may be attributed to the ability of the c ompound to expand the colony forming unit spleen subpopulation of earl y progenitors, those cells that are resistant to several DNA damaging agents and are the precursor cells essential for reconstitution of the hemopoietic system. It seems that AS101, by minimizing adverse cytoto xicity resulting from a variety of drugs, is a promising candidate for chemoimmunotherapy with cancer patients.