This study investigated: (1) the effect of Hp as a hyperthermic sensit
izer on glioma cells; and (2) the possible mechanism of hyperthermic s
ensitization by Hp using an exogenous scavenger specific to a particul
ar reactive oxygen species. Hp at nontoxic doses at 37 degrees C signi
ficantly enhanced thermal cell damage at 41.5 degrees C and above in a
dose-dependent manner. Thermal cell damage enhancement by HP was effe
ctively suppressed by the addition of beta-carotene, a singlet oxygen
scavenger, or SOD, a superoxide scavenger, but not by the addition of
mannitol or catalase. These results support the following hypothesis:
The generation of superoxide is increased in cells treated with Hp in
combination with hyperthermia. Thermal cell damage enhancement by Hp i
s probably mediated by singlet oxygen generated via superoxide in an a
lternative pathway different from that of photosensitization. Hp has p
otential as a hyperthermic sensitizer because of the following advanta
ges: (1) its dose-dependent enhancement of thermal cell damage; and (2
) the lack of toxicity at physiological temperature at doses of Hp req
uired for hyperthermic sensitization of tumour cells.