Experimental results with the combination of bleomycin plus mitomycin C

This investigation has established the following: 1. Bleomycin, in combination with mitomycin C or other quinone-containing anticancer agents, stimulated the damage to KB cells in culture. 2. In AH66 tumor-bearing rats, the simultaneous treatments of bleomycin plus mitomycin C extend the lifespan. 3. The bleomycin-induced DNA chain breakage was enhanced by the NADPH-dependent microsomal electron transport system. The enhancement was also observed at the level of isolated nuclei and cells. Vitamin K2 and mitomycin C increased breakage at the cellular level by bleomycin and NADPH. 4. Bleomycin-Cu2+ had tendency to increase the lipid peroxidation reaction by the microsomes. However, the reaction was effectively inhibited by antioxidants. 5. Bleomycin induced aldehyde formation from DNA breakage. The formation was effectively inhibited by scavenging reactions with hydralazine hydrochloride or isoniazid. The possibility of suppressing the side effect of bleomycin was discussed in relation to TBA reactive compounds.