A breath of fresh air.
نویسنده
چکیده
-The effect of combinations of the conventional chemotherapeutic agent 1-(2-chloroethyl)-3-cyclohexyl-l-nitrosourea (CCNU) and nitroimidazole radiation sensitizers was evaluated in female C3H mice. Tumour response to single-agent or combination therapy was assessed in a tumour growth-delay assay. In the KHT sarcoma the simultaneous addition of misonidazole (MISO) was found to increase significantly the tumour growth delay resulting from CCNU treatment. The observed enhancement ratios (ER) increased with MISO dose, and ranged from 1x3 to 1-9 for sensitizer doses of 0-25-1l0 mg/g. The combination of CCNU and 1-0 or 0-5mg/g MISO in the RIF-1 tumour or the MT-1 tumour produced ERs of -2-0 and -15 respectively. In the KHT sarcoma a series of other nitroimidazole sensitizers, including Ro05-9963, SR-2555, SR-2508 and metronidazole (METRO), were also evaluated at equimolar doses (5 mmol/kg) in combination with a 20mg/kg dose of CCNU. Unlike MISO, these compounds in general failed to enhance the CCNU cytotoxicity in this tumour model. However, SR-2508 did enhance the response of the RIF-1 tumour to large single doses of CCNU, though not as much as MISO. Normal-tissue toxicity was determined using peripheral white blood cell (WBC) counts 3 days after treatment. CCNU doses of 10-50 mg/kg given either alone or in simultaneous combination with 0 5 or 1-0 mg/g MISO were studied. WBC toxicity increased with CCNU dose, but the addition of MISO at either dose did not significantly enhance this normal-tissue toxicity.
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عنوان ژورنال:
- Environmental Health Perspectives
دوره 102 شماره
صفحات -
تاریخ انتشار 1994