We evaluated the usefulness of mild temperature hyperthermia (MTH) as an inhibitor of the repair of radiation-induced damage in terms of the responses of the total [= proliferating (P) + quiescent (Q)] and Q cell populations in solid tumors in vivo.
Materials and methods
SCC VII tumor-bearing mice received a continuous administration of 5-bromo-2′-deoxyuridine (BrdU) to label all P cells. They then underwent high-dose-rate (HDR) γ-ray irradiation immediately followed by MTH or administration of caffeine or wortmannin; alternatively, they underwent reduced-dose rate γ-ray irradiation simultaneously with MTH or administration of caffeine or wortmannin. Nine hours after the start of irradiation, the tumor cells were isolated and incubated with a cytokinesis blocker, and the micronucleus (MN) frequency in cells without BrdU labeling (= Q cells) was determined using immunofluorescence staining for BrdU. The MN frequency in the total tumor cell population was determined using tumors that were not pretreated with BrdU.
In both the total and Q-cell populations, especially the latter, MTH efficiently suppressed the reduction in sensitivity caused by leaving an interval between HDR irradiation and the assay and decreasing the irradiation dose rate, as well as the combination with wortmannin administration.
From the viewpoint of solid tumor control as a whole, including intratumor Q-cell control, MTH is useful for suppressing the repair of both potentially lethal and sublethal damage.
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