Enhanced radiation response of a solid tumor with the artificial oxygen carrier 'albumin-heme'.
Tumor-cell hypoxia is one of the main factors inducing radioresistance. Enhanced tumor oxygenation has previously been achieved in an animal model using the synthetic heme-based oxygen carrier 'albumin-heme' (recombinant human serum albumin-Fe cyclohexanoil heme; rHSA-FeP). The present study was done to determine whether rHSA-FeP enhances the radiation response in an experimental tumor model. Male Donryu rats and LY80, a variant of the syngenic liver ascites tumor, were used. A total of 1 x 10(6) cells were injected into the subfascial tissue of the right thigh. The rats were divided randomly into five groups: sham (tumor implantation and sham operation); rHSA-FeP; irradiation; rHSA + irradiation; and rHSA-FeP + irradiation. Six days after, under general anesthesia, intra-arterial administration of 10 mL/kg of either 5% rHSA solution or oxygenated rHSA-FeP solution at 2.5 mL/min was done and a dose of 20 Gy was given. There were significant differences in tumor growth between the sham and irradiation groups, and between the sham and rHSA-FeP + irradiation groups. Tumor growth delay was observed and differences were significant between the sham and irradiation groups, and between the irradiation and rHSA-FeP + irradiation groups. In the present study, rHSA-FeP itself had a slight effect on tumor growth without irradiation. Enhancing the effect of rHSA-FeP on the radiation response is responsible in part for the oxygen-carrying property of rHSA-FeP. In conclusion, rHSA-FeP is a candidate radiation-enhancing drug. Arterial infusion of rHSA-FeP may serve as a local oxygenation method that enhances the radiation effect.
Horinouchi
Hirohisa
H
Division of General Thoracic Surgery, Department of Surgery, Keio University, School of Medicine, Shinanomachi 35, Shinjuku-ku, Tokyo 160-8582, Japan. horinouc@sc.itc.keio.ac.jp
Yamamoto
Hisashi
H
Komatsu
Teruyuki
T
Huang
Yubin
Y
Tsuchida
Eishun
E
Kobayashi
Koichi
K
D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000528:radiation effects; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D005720:Gamma Rays; D006418:Heme / Q000737:chemistry*; D000860:Hypoxia / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism*; D010534:Peritoneal Neoplasms / Q000378:metabolism / Q000532:radiotherapy / Q000556:secondary; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D051381:Rats; D011994:Recombinant Proteins / Q000627:therapeutic use*; D012709:Serum Albumin / Q000737:chemistry*; D015996:Survival Rate; D014407:Tumor Cells, Cultured
D011838:Radiation-Sensitizing Agents; D011994:Recombinant Proteins; D012709:Serum Albumin; D006418:Heme; D010100:Oxygen