Increase of antitumor effect on bleomycin by reduced nicotinamide adenine dinucleotide phosphate and microsomes in vitro and in vivo.
The DNA chain breakage effect of bleomycin A2 on isolated nuclei was enhanced over 150-fold by the reduced nicotinamide adenine dinucleotide phosphate (NADPH)-dependent electron transport system of isolated microsomes. The enhancement of bleomycin A2-induced DNA chain breakage by NADPH was also shown at the level of the intact AH66 cells. Furthermore, it was found that the simultaneous administration of bleomycin and NADPH apparently inhibited the growth of Erhlich tumors in mice compared with the administration of bleomycin alone. These results indicate that the action of bleomycin on DNA is stimulated by the microsomal NADPH-dependent electron transport system not only in vitro but also in vivo.
D000818:Animals; D001711:Biotransformation; D001761:Bleomycin / Q000008:administration & dosage* / Q000494:pharmacology; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy*; D002467:Cell Nucleus / Q000187:drug effects; D004273:DNA, Neoplasm / Q000378:metabolism; D004359:Drug Therapy, Combination; D004579:Electron Transport / Q000187:drug effects; D008862:Microsomes, Liver / Q000378:metabolism; D009249:NADP / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology; D051381:Rats
D004273:DNA, Neoplasm; D001761:Bleomycin; D009249:NADP