The influence of tumour temperature on ischemia-induced cell death: potential implications for the evaluation of vascular mediated therapies

We have evaluated the influence of tumour temperature on the kinetics and extent of tumour cell death following induction of ischemia. Induction of ischemia in SCCVII tumours implanted subcutaneously in the back of syngeneic C3H mice results in a rapid cooling of the tumour from a resting value of 35.2°C, towards ambient temperature. In the SCCVII tumour no significant cell kill is detected in the first hour of ischemia. At longer times cell kill was detected and a survival level of 2 × 10−2 was attained after 6 h of ischemia. However, if the tumours were maintained at a temperature of 37°C following induction of ischemia a more rapid and dramatic reduction in cell survival is observed with a survival level of ∼10−5 being attained after 4 h of ischemia. Qualitatively similar results are obtained using the Lewis lung tumour implanted in C57BL mice. Similar rapid cooling following occlusion of the blood supply is observed in the C3H/TIF tumour implanted in the foot. For the C3H/TIF induction of ischemia for up to 6 h resulted in no significant growth delay provided the tumours were kept at room temperature. However, if the tumours were maintained at a temperature of 37°C during the ischemic insult significant growth delay was observed for all clamping times exceeding 1 h. These results show the importance of tumour temperature on the kinetics and extent of tumour cell kill during ischemia. This finding has particular relevance for studies in which agents known to reduce tumour blood flow are used in animals bearing superficially located tumours.