Evaluation of Inhibition of Human Tumor Tissue by Cancer Chemotherapeutic Drugs With an In Vitro Test2

Abstract

An in vitro test system is presented that allows simultaneous testing of chemotherapeutic agents on human malignant tissue. Inhibition of dehydrogenase activity by the test compound is determined in an agar suspension of the homogenized tissue. Such a test system might be useful with biopsy material, since it allows selection of an agent, if any exists, that is effective on that particular material. Comparison of results with the use of normal and tumor tissue from the same patient demonstrated the topical toxicity of compounds. The fact that the most effective compounds were also the most toxic reaffirms the lack of specificity of these compounds for malignant tissue. From examination of over-all effectiveness at one concentration of drug, both compounds and tissue sites may be ranked: 5-Fluorodeoxyuridine was effective in the largest percentage, while N,N′N″-triethylenethiophosphoramide was least effective. Amethopterin, Nitromin, and 5-fluorodeoxyuridine were consistently the most effective compounds. Bone and connective tissues were most sensitive, and hemopoietic and lymphatic tissues least sensitive. Thirty-four tissues (11%) were not affected by any drug, and many tissues responded to only one or two drugs, which indicated the general resistance of most tissues to known chemotherapeutic compounds.