HYPERTHERMIC SENSITIZATION BY THE RADICAL INITIATOR 2,2'-AZOBIS-(2-AMIDINOPROPANE) DIHYDROCHLORIDE (AAPH) .1. IN-VITRO STUDIES
HYPERTHERMIC SENSITIZATION BY THE RADICAL INITIATOR 2,2'-AZOBIS-(2-AMIDINOPROPANE) DIHYDROCHLORIDE (AAPH) .1. IN-VITRO STUDIES
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DOI：
10.3109/02656739409009348
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发表时间：
1994-03-01
影响因子：
3.1
通讯作者：
MITCHELL, JB
中科院分区：
文献类型：
--
作者：
KRISHNA, MC;DEWHIRST, MW;MITCHELL, JB
AAPH (2,2'-azobis-(2-amidinopropane dihydrochloride)) is a water-soluble, heat-labire 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 AAPK 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 9x10(-1) however, a 75 min exposure at 42 degrees C+AAPH resulted in survival of 5.5x10(-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.
