HYPERTHERMIC SENSITIZATION BY THE RADICAL INITIATOR 2,2'-AZOBIS-(2-AMIDINOPROPANE) DIHYDROCHLORIDE (AAPH) .1. IN-VITRO STUDIES

AAPH (2,2'-azobis-(2-amidinopropane dihydrochloride)) is a water-solub le, heat-labire azo compound which undergoes thermal decomposition to produce carbon-centred free radicals. These carbon-centred radicals mi ght be directly cytotoxic or may react with oxygen to produce potentia lly cytotoxic alkoxyl and peroxyl radicals. The rate of free radical p roduction as a result of AAPK thermal decomposition increases with inc reasing 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 c ells exposed to 42, 43 and 45 degrees C. For a 75 min exposure to 42 d egrees C alone? cell survival was reduced to 9x10(-1) however, a 75 mi n exposure at 42 degrees C+AAPH resulted in survival of 5.5x10(-4). Fo r 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. T hese findings would encourage in vivo evaluation of AAPH (or analogues ) as a temperature-dependent heat sensitizer. AAPH represents a new cl ass of heat sensitizers which may have use in unravelling the mechanis m(s) of heat killing and may have utility in local hyperthermia treatm ent.