Abstract
Neocarzinostatin (NCS) used for the chemotherapy of leukemia and cancers such as stomach, pancreas and bladder, has been pointed out to have the side effects mainly causing leukopenia.
In order to prevent these side effects of NCS by systemic administration, we have attempted to inject NCS directly into the tumor tissues and to inactivate NCS leaked from the tissues by the treatment of antidotes for NCS.
The present report deals with the influence of some antidotes on the toxicity of NCS in vitro and in vivo.
The results demonstrated that;
1. Four SH-compounds, such as thiopronin, glutathione (reduced form), sodium thioglycolate and L-cysteine monohydrochloride monohydrate were effective to inactivate antibacterial activity of NCS against M. luteus ATCC 9341 in vitro.
2. It was recognized that acute toxicity of NCS was reduced by pretreatment of these SH-compounds and its action was dose related. The LD50 values of NCS intravenous administration in mice increased 5.8-to 24-fold when 150, 300, 500 and 1,000 mg/kg of thiopronin were administered intravenously 2 minutes prior to NCS. And 2.3-to 4.2-fold by 500 and 1,000 mg/kg of glutathione (reduced form), 1.6-to 4.2-fold by 50,100 and 200 mg/kg of sodium thioglycolate, 1.9-to 4.2-fold by 100, 200 and 400 mg/kg of L-cysteine monohydrochloride monohydrate respectively.
3. On the other hand, pretreatment of NCS didn't affect the acute toxicity of thiopronin.
