Enhancement of ultrasonically induced cell damage by a
gallium-
porphyrin complex [
ATX-70, 2,4-bis(1-decyloxyethyl)-Ga(III)-1,3,5,8- tetramethylporphryin-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 microM
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 microM
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.