抄録
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.
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.
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.
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.
