Enhancement of Ultrasonically Induced Cell Damage by a Gallium‐Porphyrin Complex, ATX‐70

• Published in: Cancer science Vol. 84; no. 5; pp. 582 - 588
• Main Authors: Umemura, Shin‐ichiro, Yumita, Nagahiko, Nishigaki, Ryuichiro
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.05.1993; Japanese Cancer Association; John Wiley & Sons, Inc
• Subjects: Animals; Antineoplastic Agents - pharmacology; Aqueous solutions; ATX‐70; Biological and medical sciences; Bleaching; Cell damage; Electron spin resonance; Gallium; Histidine; Histidine - pharmacology; Imidazole; Male; Mannitol; Mannitol - pharmacology; Medical sciences; Mice; Mice, Inbred ICR; Nitric Oxide - metabolism; Nitroxide; Other treatments; Oxygen; Oxygen - metabolism; Porphyrins - pharmacology; Radiation; Sarcoma; Sarcoma 180 - metabolism; Sarcoma 180 - pathology; Sarcoma 180 - therapy; Singlet Oxygen; Sonochemical activity; Treatment. General aspects; Tumor Cells, Cultured; Tumors; Ultrasonic Therapy; Ultrasound; Oxygen; Sonochemistry; Rodentia; Malignant tumor; Sarcoma 180; Biological activity; Vertebrata; Experimental disease; Mammalia; Treatment; Mouse; Porphyrin; Animal; Established cell line; Singlet; Gallium complex; Ultrasound
• ISSN: 0910-5050; 1347-9032; 1349-7006; 1876-4673
• DOI: 10.1111/j.1349-7006.1993.tb00179.x

Enhancement of ultrasonically induced cell damage by a gallium‐porphyrin complex [ATX‐70, 2,4‐ bis(l‐decyloxyethyl)‐Ga(III)‐1,3,5,8‐tetramethylporphyrin‐6,7‐dipropionyl diaspartic acid] was investigated. The rate of damage to isolated sarcoma 180 cells in air‐saturated suspension induced by 2 MHz ultrasound irradiation was enhanced more than four times by 80 μM ATX‐70 in contrast to only twice by the same concentration of hematoporphyrin (Hp). The enhancement was almost completely inhibited in the presence of 10 mM histidine in the suspension, but not at all by 100 mM mannitol, which suggests that the enhanced cell damage was mostly mediated by singlet oxygen. Ultrasonically induced active oxygen generation in an air‐saturated aqueous solution of ATX‐70 was studied by detecting the electron spin resonance signals of 2,2,6,6,‐tetramethyl‐4‐piperidone‐N‐oxyl produced by the reaction of 2,2,6,6‐tetramethyl‐4‐piperidone with the generated active oxygen species. The rate of ultrasonically induced nitroxide generation was enhanced five times by 80 μM ATX‐70 in contrast to only twice by Hp. The enhancement was inhibited significantly in the presence of 10 mM histidine in the suspension, but not at all by 100 mM mannitol. The singlet oxygen generation in air‐saturated aqueous solution was further confirmed by the bleaching of N, N‐dimethyl‐4‐nitrosoaniline in the presence of imidazole. The ultrasonically induced bleaching rate was enhanced six times by ATX‐70, in contrast to only twice by Hp.