Effects of Mild Temperature Hyperthermia and p53 Status of Tumor Cells on the Size of Hypoxic Cell Fractions in Solid Tumors

Abstract

Human head and neck squamous cell carcinoma cells transfected with mutant TP53 (SAS/mp53) or with neo vector as a control (SAS/neo) were inoculated subcutaneously into both hind legs of Balb/cA nude Mice. The mice then received nicotinamide injection or carbogen gas (95% O2, 5% CO2) inhalation with or without mild temperature hyperthermia (MTH, 40 centigrade, 60 min). After each treatment, the mice received a series of test doses of gamma-rays while alive or after tumor clamping to obtain hypoxic fractions (HFs) in the tumors. SAS/mp53 tumors showed significantly larger values in the size of not only the HF but also the diffusion-limited chronically HF than SAS/neo tumors. MTH could efficiently release the chronically HF, irrespective of p53 status. These supported the fact that, in gamma-ray irradiation and cisplatin treatment, the enhancement in combination with MTH was more remarkable in SAS/mp53 cells than SAS/neo cells. [J Radiat Res 44:407 (2003)]