[Recent advanced studies on mitomycins, antitumor activity and mode of action].
Mitomycin C (MMC) showed a wide antitumor spectrum with regression of various tumors and the optimal schedule of a single or intermittent administration against human tumor cells xenografted to nude mice, confirming the early reports obtained in rodent tumor system. The sensitivity of various human tumors xenografted to nude mice has been tested to antitumor agents to establish the system which could select the clinically active drugs. The effectiveness of MMC against human stomach cancers xenografted to nude mice clearly correlated to the clinical effect of MMC against gastric cancer. The covalent cross-link adducts between MMC and DNA were isolated in the bioreductive system of NADPH-cytochrome C reductase and NADPH, and the major monoadduct was determined as N2-(2'' beta 7'-diaminomitosen-1''-alpha yl)-2'-deoxyguanine. Importantly, bisadduct was isolated, and the structure was determined by spectroscopic method. DNA-DNA cross-link formation was shown by alkaline elution in cells treated with MMC. The activation of MMC has been characterized by the two electron transfer process, however, the one electron transfer process was proposed by electrochemical analysis. MMC was effective against hypoxic cells. Several cell lines resistant to MMC were isolated, and some MMC derivatives showed in vivo and in vitro anti-tumor activity against these resistant cells.
D000818:Animals; D002460:Cell Line; D003110:Colonic Neoplasms / Q000188:drug therapy; D006801:Humans; D007941:Leukemia P388 / Q000188:drug therapy; D016685:Mitomycin; D008937:Mitomycins / Q000494:pharmacology / Q000627:therapeutic use*; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000188:drug therapy; D012004:Rectal Neoplasms / Q000188:drug therapy; D013274:Stomach Neoplasms / Q000188:drug therapy; D013329:Structure-Activity Relationship
D008937:Mitomycins; D016685:Mitomycin