マウス固形腫ように対する｀ｌ９５ｍ´Ｐｔ‐ＣＤＤＰを用いた温熱化学療法におけるニコチンアミドの付加的効果に関する考察

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  • Additional Effect of Nicotinamide on Thermochemotherapy Using l95mPt-CDDP for Murine Solid Tumors.

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It is known that nicotinamide, one of blood flow modifiers, can eliminate acutely hypoxic cells in solid tumors. In this work, to study combined effects of hypeprthermia and nicotinamide in chemotherapy with cis-diamminedichloroplatinum (II) (CDDP), the influence of intraperitoneally administered nicotinamide on uptake of CDDP in murine solid tumors using 195mPt-labeled CDDP and on cell survival using colony formation assay was examined. SCC VII and EMT6/KU tumors transplanted in the hindlegs of C3H/He and Balb/c mice were used. Nicotinamide was intraperitoneally injected 60 and 90 minutes before the administration of CDDP, and the doses of 0.05-0.5 LD50 of 195mPt-CDDP were given intraperitoneally. One hour later, heating at the temperature of 42°C was performed in vivo to tumor of the left limb by water-bath for 30 minutes. One hour after the treatment, mice were sacrificed and then the tumors were excised and trypsinized. The concentration of CDDP in the tumor cells was measured by gamma-counter, and the cell survival assay was performed using in vivo-in vitro assay method. On both tumor systems, the uptake doses of 195mPt-CDDP in the tumor cell increased in combination with hyperthermia, and combined with or without hyperthermia, intraperitoneal administration of nicotinamide also increased the uptake doses, especially in the SCC VII tumor. In the cell survival assay, in combination with the administration of nicotinamide or hyperthermia, the surviving fractions for both tumor cells decreased, especially in the SCC VII tumor again. These results were thought to be compatible with the fact that the SCC VII tumor has larger acutely hypoxic fraction than EMT6/KU tumor. Nicotinamide administration before chemotherapy combined with or without hyperthermia was thought to be effective on tumor control, especially in such tumors including large acutely hypoxic fractions as the SCC VII tumor.

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