ニトロソウレア系制癌剤 ACNU, MCNUの実験脳腫瘍に対する抗腫瘍効果の比較検討

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  • Comparative Studies on Anti-tumor Effects of Nitrosoureas, ACNU and MCNU, on Experimental Brain Tumors

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Comparative anti-tumor effects of ACNU and MCNU were studied on 20-methylcholanthrene-induced C57 black mouse malignant gliomas (MG-cells) and rat glial tumors (C6-cells) in vitro and in vivo.<BR> The inhibitory effects of ACNU and MCNU in vitro were dependent on dose and time. The concentration showing inhibitory effect was more than 10 μg/ml. ACNU was a slightly more effective than MCNU. ACNU significantly inhibited DNA synthesis at concentrations higher than 10 μg/ml, but had no such effect on RNA and protein syntheses. MCNU also inhibited DNA synthesis similar to but less than that of ACNU.<BR> By a single intraperitoneal administration on day 5, an increased life span (ILS) was observed with ACNU (120.3 % increase) and with MCNU (100.4%). The optimal dosis was 25 mg/kg/day for both drugs. The therapeutic ratio, or optimal dose divided by the dose producing an increased life span of 30% over controls, of ACNU was 4.17 and that of MCNU was 6.67. When 25 mg/kg/day of ACNU was administered intraperitoneally on day 5, two out of 10 mice survived over 60 days. In case of MCNU, one out of 10 mice survived. A single administration of ACNU or MCNU was more effective for the increased life span compared with intermittent administration.<BR> From these results, it is suggested that the new water soluble nitrosourea, MCNU, can be utilized as a chemotherapeutic agent against brain tumors as in the case of ACNU.

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