Hyperthermic sensitization by the radical initiator 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH). I. In vitro studies.

AAPH (2,2'-azobis-(2-amidinopropane dihydrochloride)) is a water-soluble, heat-labile azo compound which undergoes thermal decomposition to produce carbon-centred free radicals. These carbon-centred radicals might be directly cytotoxic or may react with oxygen to produce potentially cytotoxic alkoxyl and peroxyl radicals. The rate of free radical production as a result of AAPH thermal decomposition increases with increasing temperature. We have evaluated the efficacy of AAPH as a heat sensitizer for Chinese hamster V79 cells by the clonogenic assay. AAPH (50 mM) was not cytotoxic to V79 cells at 37 degrees C for exposures up to 3 h. In contrast, AAPH (50 mM) was found to markedly sensitize cells exposed to 42, 43 and 45 degrees C. For a 75 min exposure to 42 degrees C alone, cell survival was reduced to 9 x 10(-1); however, a 75 min exposure at 42 degrees C+AAPH resulted in survival of 5.5 x 10(-4). For 43 and 45.5 degrees C heating, cell survival was potentiated by AAPH at the 1% survival level by 4.1 and 1.4-fold, respectively. AAPH was also found to sensitize both hypoxic cells and thermotolerant cells. These findings would encourage in vivo evaluation of AAPH (or analogues) as a temperature-dependent heat sensitizer. AAPH represents a new class of heat sensitizers which may have use in unravelling the mechanism(s) of heat killing and may have utility in local hyperthermia treatment.

Duke Scholars

Author Mark Wesley Dewhirst Radiation Oncology

Author Henry Seth Friedman Neurosurgery, Neuro-Oncology