Influence of ultrasound-induced hyperthermia and X-irradiation on the incidence of metastases from a solid tumor.

The KHT sarcoma transplanted into mouse legs was treated by X-irradiation, hyperthermia or a combination of X-irradiation plus hyperthermia. Neither 20 Gy of X-irradiation or hyperthermia for 60 min were effective in controlling the local tumors when used alone. Simultaneous treatments, however, resulted in 22% of the tumors being locally controlled corresponding to a TER of 2.0. Local control was increased when irradiation was given 1 h before or after hyperthermia, TER 2.8 and was maximum, TER 2.9, when the hyperthermia was 0.1 h after irradiation. When the local tumor was controlled by irradiation alone or by irradiation delivered 1 h before or after hyperthermia, all of the metastases that subsequently occurred arose before or during treatment. When tumors were locally controlled by radiation given during or immediately after hyperthermia, metastases developed that must have occurred as a consequence of the treatment. The treatment sequence that resulted in a maximum TER for tumor control did not correlate with the risk of metastatic spread. The timing of the irradiation in relation to hyperthermia may explain some contradictory findings regarding the influence of heat on the incidence of metastases. Hyperthermia did not affect the distribution of anatomic sites involved with metastases or the ratio of lymphatic to hematogenously spread metastases.

Copper chelator enhancement of bleomycin cytotoxicity.

Bleomycin's effects on DNA strand scission are inhibited by low concentration of some metal ions (including copper), greatly stimulated by ferrous (Fe+2) ions, and increased and probably mediated by the production of superoxide radicals (O2-), hydroxyl radicals (OH), and hydrogen peroxide (H2O2). However, the role of these mechanisms in overall bleomycin cytotoxicity is not known. For this reason, we have treated the Chinese hamster cell line (V79) cells with a copper chelator, diethyldithiocarbamate (DDC) and bleomycin in vitro DDC is known to inhibit superoxide dismutase (SOD), an enzyme responsible for the scavenging of O2-. The cytotoxicity is determined by the standard clonogenic survival method, which shows that DDC treated cells are more susceptible to bleomycin either as a function of bleomycin dose or as a function of bleomycin treatment time. These results support the notion that reducing Cu2+ levels and/or increasing O2- concentrations can modify the cytotoxicity of bleomycin.