Effect of combined ascorbic acid and B-12 on survival of mice with implanted Ehrlich carcinoma and L1210 leukemia.

A combination of dehydroascorbic acid and hydroxycobalamin (vitamin B-12) inhibited mitoses of tumors in mice. The present study was performed to test the effect of these vitamins on the survival of mice bearing carcinomas and leukemias. In each assay 40 mice received 0.1 mL ip tumor cells (x10(5)). After 24 h, 20 mice were injected with 0.2 mL (0.4 g/kg body wt) of the vitamins daily for 10 d. All controls died by day 19, but greater than 50% of the treated mice were alive after 60 d. In vitro findings revealed inhibition of mitoses in L1210 leukemia cells, but not in normal L929 cells. In recent research with cobalt-ascorbate plus vitamin C, we demonstrated that when B-12 is combined with vitamin C, the cobalt nucleus of B-12 attaches to a carbon on vitamin C, forming cobalt ascorbate. Tests proved that cobalt ascorbate plus vitamin C also inhibited tumor cells.

Mitogenic inhibition and effect on survival of mice bearing L1210 leukemia using a combination of dehydroascorbic acid and hydroxycobalamin.

The present study was designed to test the effect of a combination of dehydroascorbic acid (DHA) and hydroxycobalamin (vitamin B12) on the survival of mice bearing L1210 leukemia. Results showed a significant increase in survival of treated mice compared with controls (p less than or equal to 0.0001) (Student's t-test). This positive effect was significantly lost when DHA was substituted by ascorbic acid (AA) in the same experimental conditions. In vitro findings also revealed that the DHA-B12 combination specifically inhibited mitoses of L1210 cells while non-neoplastic L929 cells were not affected.

Inhibiting effect of dehydroascorbic acid on cell division in ascites tumors in mice.

The transplantable murine ascites tumors, P388 leukemia and Ehrlich carcinoma, demonstrated complete inhibition of mitotic activity after treatment with dehydroascorbic acid in mice. Citric acid at the same pH value (2.4), however, showed no diminution of mitoses. Microscopic examination of the stained ascites exudate taken from the mice treated with 10 mg dehydroascorbic acid revealed few tumor cells and a pronounced increase in white blood cells, whereas the ascites tumor exposed to citric acid appeared normal.

Inhibiting effect of vitamins C and B12 on the mitotic activity of ascites tumors.

The mitotic activity of the transplantable mouse tumors, Sarcoma 37, Krebs-2, and Ehrlich carcinomas, in the ascites form, were inhibited after treatment with a mixture of vitamins C and B12 with no apparent toxic side effects. These vitamins when administered alone, at the same dosage, did not seem to have any apparent effect on mitosis or the morphology of the cells studied. Microscopic examination of the stained ascites fluid taken from the mice treated with the vitamin mixture showed few tumor cells, and these in various stages of disintegration. Also, an increase in lymphocytes, monocytes and neutrophils were noticed; however, later in the experiment, no tumor cells could be found and monocytes and macrophages were abundant.

Response of neoplastic and non-neoplastic cells to a yeast extract.

PCO, an aqueous-alcoholic extract of the yeast, Saccharomyces cerevisiae, was found to inhibit mitoses of 4 different ascites tumors removed from mice. Carried as established in vitro lines 6 tumors and 4 established lines of non-neoplastic cells could not be inhibited by PCO. Primary cultures (diploid) of mouse embryo tissue cells and granulocytic blast cells from adult mice also could not be mitotically inhibited by PCO.

Selective effect of fractions of a yeast extract (PCO) on normal and malignant cells.

The selective action of two fractions of PCO (a yeast extract) on normal and malignant cells was demonstrated. In vivo, the mitotic activity of malignant cells was inhibited by the methanol-insoluble fraction of PCO, whereas the methanol-soluble fraction caused no inhibition. The in vitro studies, however, showed inhibition of mitoses with both fractions. The malignant cells employed in vitro and in vivo were the Krebs-2 and Ehrlich carcinomas. The nonneoplastic cells tested in vitro were established cultures of epithelial-like cells from murine bone marrow and thymus, and corneal epithelium and peripheral blood in vivo.

Offsetting toxicity of antineoplastic agents.

PCO, a yeast extract, offsets at least in part the mitotic inhibitory effect of methotrexate and fluorouracil on bone marrow cells in vitro but increases the antimitotic activity of the drugs on ascites Krebs-2 carcinoma under similar conditions. In vivo, PCO enhances the action of methotrexate against the L-1210 lymphoid leukemia and does not interfere with the effectiveness of fluorouracil against the ascites Krebs-2 tumor.

Antimitotic agents and tumor regression.

The selective action of nonantigenic tissue extracts on malignant cells was demonstrated using tissue culture techniques. The mitotic index of three strains of neoplastic cells was significantly reduced by the use of extracts which previously had proven effective in adversely affecting the development of spontaneous neoplasms. Under the same conditions the division rate of normal cells in tissue culture was not affected by the extracts. The malignant cells used were the Krebs 2, Sarcoma 180 and the L1210 leukemia. The normal cells were the L929 fibroblasts and epithelial-like cells from bone marrow and corneal tissue.