HYPERTHERMIA, RADIATION CARCINOGENESIS AND THE PROTECTIVE POTENTIAL OF VITAMIN-A AND N-ACETYLCYSTEINE

The in vivo carcinogenic risk of hyperthermia, alone or in combination with irradiation, and the anti-carcinogenic potential of vitamin A an d N-acetylcysteine (AcCys) were investigated. Starting 1 month before treatment, 160 rats were divided into four diet groups: no additives, vitamin A-enriched diet, AcCys and the combination vitamin A + AcCys. In 10 animals per diet group, the hind leg was treated with either X-i rradiation alone (16 Gy), hyperthermia alone (60 min at 43 degrees C), hyperthermia 5 h prior to irradiation or hyperthermia 5 h after irrad iation. Animals were observed for 2 years after treatment with regard to the development of tumours either inside or outside the treated vol ume. After 16 Gy alone 12 +/- 5% of the animals developed a tumour. Tu mour incidence increased to 37 +/- 9% (borderline significance P = 0.0 7 versus treatment with X-rays alone) when hyperthermia was applied pr ior to X-rays, and to 24 +/- 8% (NS) with hyperthermia after irradiati on. The relative risk ratio (RRR) for tumour induction was increased t o 2.4 by hyperthermia if combined with X-irradiation. Pathological cha racterization of induced tumours showed that these were of the fibrosa rcoma, osteosarcoma and carcinoma type. Vitamin A alone or in combinat ion with AcCys slightly protected against the induction of tumours by X-rays without or with hyperthermia (RRR of 0.4). However, morphologic al changes such as lipid accumulation in hepatocytes and damage to the parenchyma were noticed in livers from all animals that were given a vitamin-A-enriched diet (P < 0.0001). Data from the present and past r eports show that hyperthermia alone is not carcinogenic, but that it m ay increase radiation carcinogenesis. Treatment temperature and time o f exposure to heat in addition to the radiation dose applied are impor tant factors in the carcinogenic process. The enhancement of radiation carcinogenesis seems to occur independently of the sequence and time interval between irradiation and hyperthermia. However, not all data a re consistent with this interpretation.