Bioreduction of RSU 1069 and mitomycin C after dearterialization.
RSU 1069 (1-(2-nitro-1-imidazolyl)-3-(1-aziridinyl)-2-propanol) and Mitomycin C (MMC) have both been shown to be directly cytotoxic to hypoxic cells. Repeat and transient dearterializations of a liver tumour would cause its cells to become intermittently hypoxic. In this experiment the therapeutic gain of RSU 1069 and MMC was evaluated when combined with either a single or repeat dearterializations of a transplanted liver tumour. The tumour growth during the first 6 days was significantly delayed when the administration of RSU 1069 (40 mg kg-1, i.p.) was followed 15 minutes later by a single dearterialization for 2 hours compared with sham operation (P = 0.0369) or either treatment alone (P = 0.0142 vs RSU 1069 alone and P = 0.0031 vs a single dearterialization for 2 hours alone). Furthermore, RSU 169 administered 15 min prior to a single dearterialization for 2 hours is more effective to retard tumour growth than MMC either alone (P = 0.0198) or with the same period of dearterialization (P = 0.0326). Repeat dearterializations (2 hours/day) during 5 days effectively retarded the growth of the tumour by itself (P = 0.015 vs sham operation). A larger growth delay was obtained when RSU 1069 was administered 15 min before the first dearterialization (P = 0.009 vs sham operation), though the growth delay between those two groups was not significant (P = 0.07). Survival time was significantly prolonged when repeat dearterializations were combined with RSU 1069 (P = 0.007 vs sham operation; P = 0.0009 vs RSU 1069 and P = 0.003 vs repeat dearterialization alone).(ABSTRACT TRUNCATED AT 250 WORDS)
Wang
L Q
LQ
Department of Surgery, Lund University, Sweden.
Persson
B G
BG
Bengmark
S
S
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015687:Cell Hypoxia; D017024:Chemotherapy, Adjuvant; D006499:Hepatic Artery / Q000601:surgery*; D006801:Humans; D008026:Ligation; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000601:surgery*; D008297:Male; D008920:Misonidazole / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016685:Mitomycin / Q000627:therapeutic use*; D051381:Rats; D011920:Rats, Inbred WF
D000970:Antineoplastic Agents; D016685:Mitomycin; C041712:1-(2-nitro-1-imidazolyl)-3-aziridino-2-propanol; D008920:Misonidazole