Quantitative Biochemical Differences between Tumor and Host as a Basis for Cancer Chemotherapy

Abstract

6,7-Dimethyl-9-hydroxyethyl-isoalloxazine (U-2113), an analog of riboflavin, was observed to have very weak carcinostatic action when used alone against the adenocarcinoma 755 grown in either sex of the C57BL mouse. Chemotherapeutic trials employing 8-azaguanine and testosterone in double combination, or with the addition of either deoxypyridoxine or U-2113 to give a triple combination, produced no greater carcinostatic effect than could be produced by 8-azaguanine alone under the particular conditions of these experiments. However, the combination of all four of these compounds produced a significant increase in carcinostatic action. The increase in carcinostasis resulting from the combining of 8-azaguanine, testosterone, U-2113, and deoxypyridoxine was achieved with doses of U-2113 and deoxypyridoxine which by themselves would be ineffective in producing toxic effects on either tumor or host tissue. The riboflavin analog, U-2113, does not antagonize the flavo-enzyme, xanthine oxidase, in the 755 tumor. Total riboflavin, flavin adenine dinucleotide (FAD), flavin mononucleotide (FMN), and free riboflavin were measured in the adenocarcinoma and host tissues of the mice (C57). Riboflavin was found to be significantly lower in tumor than any normal tissue analyzed except skeletal muscle. The ratio of FAD to total riboflavin of tumor was very similar to that of other tissues, while the ratio of FMN to total riboflavin of various normal tissues covered a wide range which included tumor.