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Development of Thermotolerance during Fractionated Hyperthermia in a Solid Tumor in Vivo¹

The Institute of Cancer Research, Radiumstationen, 44 Nörrebrogade [T. K., O. S. N., J. O.], and the Institute of Theoretical Statistics, University of Aarhus [A. H. A.], DK-8000 Aarhus C, Denmark

The effect of 43.5° water bath heating on a C3H mammary carcinoma inoculated into the foot of BALB/c x DBA F₁ (hereafter called CD2F₁ mice was investigated. A single heat treatment resulted in a linear dose-response relationship between heating time and tumor growth time (i.e., the time for tumors to reach 5 times the initial volume of the first treatment day). Recovery from hyperthermic damage, demonstrated by two-dose fractionation experiments (30 min + 60 min at 43.5°), increased with increasing fractionation interval and reached its maximum at a 16-hr interval. Preheating for 30 min at 43.5° induced thermal resistance to a second heat treatment at 43.5° (thermotolerance) which was evidenced by a decrease in the slope of the dose-response curves. This thermotolerance gradually increased with increasing interval and reached a maximum at a 16-hr interval with a thermotolerance ratio of 5.2. Subsequently, the thermotolerance gradually decayed and completely disappeared at a 120-hr interval. No detectable repair of hyperthermic damage was found in this tumor. In principle, these data confirm the observations on thermotolerance reported previously for cell cultures in vitro and for several normal tissues in vivo.

¹ This work was supported by the Danish Cancer Society (Grants 24/79 and 87/79) and Ingeborg and Leo Danins Foundation for Scientific Research. Presented in part at the 7th Meeting of the Nordic Society for Radiation Research and Radiation Technology March 8 to 11, 1981, Gol, Norway.

² This work was performed during a fellowship under the Ministry of Education in Denmark. Present address: Department of Obstetrics and Gynecology, School of Medicine, Kyushu University, Fukuoka City 812, Japan.

³ To whom requests for reprints should be addressed.

Received 6/25/81. Accepted 12/ 8/81.

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