Vitamin C has been suggested and disputed as an anti-cancer agent. For cells in culture, no preferential effect against any type of cancer has yet been demonstrated. Our aim here is to show that vitamin C is selectively toxic to at least one type of malignant cell--a melanoma--at concentrations that might be attained in humans. Copper ions react with ascorbate and generate free radicals in solution. Ascorbate when combined with copper rapidly reduces the viscosity of DNA solutions and has exhibited some carcinostatic effects on transplanted sarcoma 180 tumours in mice. We reasoned that the elevated copper concentration in melanoma could result in a more selective toxicity for ascorbate.

SUMMARYHPA 39 is a tungsto-antimoniate compound, closely related to the mineral consensed ion HPA 23, from which it differs only by the presence of a potassium instead of a sodium ion inside the central cage. A single parenteral injection of HPA 39 on the same day as virus inoculation decreased the splenomegaly induced by Friend virus in DBA/2 mice and protected 90% of the infected animals against leukaemia. It also lowered the virus content in spleen extracts compared to untreated animals. The efficiency of treatment with HPA 39 on leukaemic mice at a late stage of the disease suggested that the compound may act at the cellular level as well as by inducing virus growth inhibition. HPA 39 also induced an early decrease of peripheral blood reticulocytes, and of the most differentiated erythroblasts in the bone marrow 1 day after injection of the compound. Mineral condensed ions therefore appear to have multiple biological effects both in vitro and in vivo. I N T R O D U C T I O NThe antiviral activity of mineral condensed ions (MCI) has been evidenced by several investigators. To date, HPA 23 (5-tungsto-2-antimoniate) has been the most active MCI in both in vitro and in vivo studies (Jasmin et aL, 1974a, b;Werner et aL, 1976;Tsiang et al., 1978). HPA 23 has a mol. wt. of 6800 and has a trimeric structure which is characterized by a central cage maintained by a sodium ion. In order to elucidate the relationship between the structure and the mode of action of the MCI, we have extensively investigated the antiviral activity of HPA 39, another MCI with a central cage. HPA 39 also belongs to the group of tungsto-antimoniates (21-tungsto-9-antimoniate). However, it differs from HPA 23 by the presence of a potassium ion instead of a sodium ion in the central cage. We report a number of experiments which demonstrate the anti-leukaemic activity of HPA 39 in Friend leukaemia. M E T H O D SHPA 39. HPA 39 was prepared by mixing a tungstate solution with an antimonycontaining solution. The tungstate solution was obtained by mixing 81 g tungsten oxide (WO3) with 40 g solid KOH in 200 ml distilled water. The antimony-containing solution was obtained by dissolving 21.8 g antimony oxide (9b202) in 100 ml 6 M-HC1 and neutralizing with 30 g solid KHCO 3. The antimony solution was then gradually added to the tungstate solution kept at 80 °C. After cooling, a tungsto-antimoniate precipitate was obtained which was recrystallized from distilled water.

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Two continuous cell lines derived from long-term cultures of AKR mouse bone marrow adherent cells were isolated. These cell lines release colony stimulating activity (CSA), a factor that induces in vitro differentiation of granulocyte-macrophage progenitor cells. The colony forming cells and cluster forming cells in mouse marrow responsive to CSA from mouse lung conditioned medium MLCM). Colony forming cells were characterized by analysis of their density distribution after equilibrium centrifugation in density gradient. Cluster forming cells were characterized by analyzing the progeny of individual clusters after transfer to fresh semisolid culture medium containing MLCM. The results obtained indicate that the CSA from cell line conditioned medium closely compares with the CSA from MLCM in terms of the populations of colony and cluster forming cells stimulated.