Development of a new treatment of liver tumor utilizing active oxygen species.

Research Project

Project/Area Number	62570586
Research Category	Grant-in-Aid for General Scientific Research (C)
Allocation Type	Single-year Grants
Research Field	Digestive surgery
Research Institution	Asahikawa Medical College
Principal Investigator	ASAKAWA Hiroichi Asahikawa Medical College, Assistant, 医学部, 助手 (80125393)
Co-Investigator(Kenkyū-buntansha)	HAYASHI Hirokazu Asahikawa Medical College, Assistant, 医学部, 助手 (90133834) KUSANO Mituo Asahikawa Medical College, Assistant Professor, 医学部, 講師 (70091569)
Project Period (FY)	1987 – 1988
Project Status	Completed (Fiscal Year 1988)
Budget Amount *help	¥2,000,000 (Direct Cost: ¥2,000,000) Fiscal Year 1988: ¥1,000,000 (Direct Cost: ¥1,000,000) Fiscal Year 1987: ¥1,000,000 (Direct Cost: ¥1,000,000)
Keywords	Liver ischemia / Oxygen free radicals / Xanthine oxidase / 抗腫瘍効果 / 肝細胞 / 低酸素障害 / Superoxide Dismutase
Research Abstract	Implication of oxygen derived free radicals on ischemic and reperfusion injury of the liver was studied by using in vitro and in vivo models. Viability of hypoxic hepatocytes induced by blowing the mixed gas of 95% nitrogen + 5% carbon dioxide to a culture medium was regained by adding oxygen redical scavenger, Superoxide Dismutase, to the medium. Survival of the ischemically induced liver failure rats was also improved by pretreatment with Allopurinol, a specific xanthine oxidase inhibitor. Several parameters of ischemic liver damage such as aspartate aminotransferase(ASAT), alanine aminotransferase (ALAT), -hexosaminidase, hepaplastin test, hepatic tissue water content and histology were also improved by allopurinol administration. Malondialdehyde which is produced by free radical reaction of lipid peroxidation was suppressed by Allopurinol. All these findings support the hypothesis that oxygen derived free radicals are one of the mediators of ischemic and reperfusion liver injury and they can be produced through xanthine oxidase reaction. The suppressive effect of oxygen free redicals on tumor growth was tested by using implantable rabbit tumor model. Hypoxanthine and xanthine oxidase were separately infused to the artery supplying the tumor. The reduction of the tumor volume was not observed at 24 hours after infusion. Histlogically in hypoxanthine and xanthine oxidase infused group, massive confluent tumor necrosis with scattered islands of viable tumor cells was observed. On the other hand clumps of viable tumor cells were constantly seen in control group. These data show that oxygen free radicals have potential for the treatment of cancer.