Studies of methyl 2-nitroimidazole-1-acetohydroxamate (KIN-804) 1: effect on free radical scavenging system in mice bearing Ehrlich ascites carcinoma.
Methyl 2-nitroimidazole-1-acetohydroxamate (KIN-804) is a 2-nitroimidazole derivative containing a hydroxamate side chain designed to enhance the radiosensitization response of hypoxic cells. The possible sensitization of tumor tissue by KIN-804 can be evaluated through investigation of the levels of the free radical scavengers; namely, glutathione (GSH) and its complex enzyme system including glutathione reductase (GR) and glutathione peroxidase (GSH-Px), as well as glucose-6-phosphate dehydrogenase (G-6-PD). Female albino mice were inoculated with Ehrlich carcinoma in the thigh. Administration of KIN-804 (i.p. 80 mg/kg body weight) was carried out 20 min before localized irradiation of 10 Gy. The data revealed that KIN-804 administration, followed or not by gamma irradiation, resulted in a significant decrease in GSH content in tumor tissues associated with inhibition in GR and G-6-PD activities. Blood GSH-Px was enhanced in tumor inoculated mice and the administration of KIN-804 returned it to the normal value. These changes were more noticeable in tumor bearing mice exposed to both KIN-804 and irradiation.
Abu-Zeid
M
M
Department of Cancer Biology, National Cancer Institute, Cairo University, Egypt.
Hori
H
H
Nagasawa
H
H
Uto
Y
Y
Inayama
S
S
D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism*; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism / Q000528:radiation effects; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism / Q000528:radiation effects; D005980:Glutathione Reductase / Q000378:metabolism / Q000528:radiation effects; D006877:Hydroxamic Acids / Q000494:pharmacology*; D051379:Mice; D009593:Nitroimidazoles / Q000494:pharmacology*; D010084:Oxidation-Reduction; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*
D016166:Free Radical Scavengers; D006877:Hydroxamic Acids; D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; C076264:2-nitroimidazole-1-methylacetohydroxamate; D005954:Glucosephosphate Dehydrogenase; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D005978:Glutathione