Effect of intestinal hyperthermia in the Chinese hamster

If hyperthermia is to become a useful cancer therapeutic modality, normal tissue response must be thoroughly understood. The hyperthermia response of Chinese hamster intestine was studied by immersion of the exteriorized small intestine in heated tissue culture medium. After heating, the small intestine was reinserted, the incision closed, and animals observed until death. Animals exposed to 42.5 degrees, 43.5 degrees, or 44.5 degrees C intestinal hyperthermia exhibited LD50/7 values (including 95% intervals) of 56 min (52.9-59.3), 29 min (26.4-31.8), or 14 min (13.2-14.6), respectively. An Arrhenius plot of LD50/7 vs 1/T degree K exhibited an inactivation energy of 139 kcal/mole, which corresponds well with values generally reported for cellular inactivation. Hamster intestine conditioned with a sublethal exposure of 8 min at 44.5 degrees C developed thermotolerance to subsequent 44.5 degrees C hyperthermia. Thermotolerance induction was maximal by 24 hr; the LD50/7 for the second dose of hyperthermia increased from 6 min at 44.5 degrees C at zero time to 21 min at 44.5 degrees C after a treatment interval of 24 hr (thermotolerance ratio of 3.5). The LD50/7 subsequently decreased from 21 min to 12 min at 44.5 degrees C (the control value) by 96 hr. The hyperthermia response of this tissue was predicated by previous results from the Chinese hamster ovary (CHO) fibroblast cell line in tissue culture, and is also similar to several mouse normal tissues.