Effects of the mode of administration of mitomycin on tumor and marrow response and on the therapeutic ratio.

The antineoplastic and toxic effects of mitomycin (MC) administered as a single pulse injection were compared with the effects of MC given as infusions over 2, 5, or 24 hours and with the effects of the drug administered in fractionated regimens incorporating 2-20 injections. The antineoplastic effects of MC were assessed using EMT6 mouse mammary tumors implanted in BALB/c mice; tumor response was assessed using both cell survival and tumor growth assays. The host toxicity of MC was assessed by measuring the survival of bone marrow stem cells (CFU-S) and by determining LD50/30's (which reflect primarily marrow injury).

Reactions of tumors and normal tissues in mice to irradiation in the presence and absence of a perfluorochemical emulsion.

The effect of pre-treatment with the perfluorochemical emulsion, Fluosol-DA, on the radiation response of normal tissues and EMT6 mammary tumors in BALB/c mice was examined. Pre-treating tumor-bearing mice with .015 ml/g of Fluosol and 30 min of carbogen (95% O2/5% CO2) increased the number of tumor cells killed by irradiation with doses of 2.

Effect of 1-methyl-5-sulfonamide-4-nitroimidazole and 1-methyl-5-bromide-4-nitroimidazole on the radiosensitivity of EMT6 tumor cells.

The compounds 1-methyl-5-sulfonamide-4-nitroimidazole and 1-methyl-5-bromide-4-nitroimidazole are extremely effective radiosensitizers of hypoxic cells in vitro. Preincubation of hypoxic cells with these and related drugs produces greater sensitization than is obtained with short incubations or is expected from the electron affinities of the compounds. The experiments reported here were undertaken to determine whether these agents were effective in sensitizing the naturally occurring hypoxic cells of solid tumors in mice.

Effect of a perfluorochemical emulsion on the development of artificial lung metastases in mice.

Intravenous infusions of perfluorochemical emulsions, combined with administration of inspired oxygen or carbogen have been found to improve tumor oxygenation and increase the response of solid tumors in animals to radiotherapy. Fluosol-DA 20 per cent, the only perfluorochemical emulsion currently approved for testing in humans in the United States, has recently entered clinical trials as an adjunct to radiotherapy in the treatment of head and neck carcinoma. The studies reported here were undertaken as part of our laboratory evaluation of the safety and clinical potential of this oxygen-transport fluid as an adjunct to cancer therapy; they asked whether single or multiple treatments with Fluosol and an oxygen-enriched atmosphere produced immunologic perturbations, pulmonary damage, or other effects which altered the development of artificial lung metastases in experimental animals.

Enhancement of artificial lung metastases by misonidazole.

The effect of treatment with the hypoxic cell radiosensitizer misonidazole on the formation of artificial lung metastases was examined. Both single treatments with large doses of misonidazole and fractionated treatments with smaller doses of misonidazole were found to increase the number of lung tumors developing after intravenous injection of EMT6 mouse mammary carcinoma cells. The immunologic and physiologic effects of the nitroimidazole were postulated to be responsible for the enhancement of lung tumor formation.