Induction of Mitotic Synchrony by Intermittent Hyperthermia in Ehrlich Carcinoma in vivo

Abstract

THE radiosensitivity of cultured neoplastic cells is generally highest during the mi to tic stage of the life cycle^1,2; their sensitivity to chemotherapeutic agents is dependent on cell age in the division cycle^3–7. If a method were devised for tumour systems in vivo to prolong the time when cells remain in mitosis or to synchronize mitotic activity in a predictable manner, the cell killing efficacy of ionizing radiation might be improved. If the same method could produce increased synchronization in any other phase in which cells are most sensitive to chemotherapeutic agents, an increased efficacy of these drugs might also result². Techniques used in vitro to obtain synchronous populations involve selective harvesting⁸, the use of chemicals^8,9 and the use of temperature^10–12. Most in vivo synchronization attempts involve the administration of drugs which disturb cell progression. The pharmacodynamics of such treatments tend to limit severely the degree of synchrony attained. Recently, 33–38% synchrony has been reported for intestinal crypt cells in vivo, following mitotic combination drug treatment with arabinosylcytosine and colcemid¹³. Martin and Schloerb¹⁴ increased significantly the mitotic activity of Walker 256 carcinoma cells in rats by intermittently raising the body temperature. If this technique proved to be reliable and the response predictable, the clinical implications are obvious. Radiotherapy during the mitotic interval of a synchronized population could result in increased cell killing with a possible decrease in the total dose, dose per fraction or concomitant number of fractions in a standard radiotherapy regime. These advantages could lead to more effective local tumour control with an increased therapeutic ratio.