Krishna M C, Dewhirst M W, Friedman H S, Cook J A, DeGraff W, Samuni A, Russo A, Mitchell J B
Radiation Biology Branch, National Cancer Institute, NIH, Bethesda, MD.
Int J Hyperthermia. 1994 Mar-Apr;10(2):271-81. doi: 10.3109/02656739409009348.
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.
2,2'-偶氮二(2-脒基丙烷)二盐酸盐（AAPH）是一种水溶性、热不稳定的偶氮化合物，它会发生热分解产生以碳为中心的自由基。这些以碳为中心的自由基可能具有直接细胞毒性，或者可能与氧反应生成潜在的细胞毒性烷氧基和过氧自由基。由于AAPH热分解产生自由基的速率随温度升高而增加。我们通过克隆形成试验评估了AAPH作为中国仓鼠V79细胞热敏化剂的效果。在37℃下暴露长达3小时，50 mM的AAPH对V79细胞无细胞毒性。相比之下，发现50 mM的AAPH能显著使暴露于42、43和45℃的细胞敏感化。单独暴露于42℃ 75分钟，细胞存活率降至9×10⁻¹；然而，在42℃+AAPH条件下暴露75分钟，存活率为5.5×10⁻⁴。对于43℃和45.5℃加热，在1%存活率水平下，AAPH分别使细胞存活率提高了4.1倍和1.4倍。还发现AAPH能使缺氧细胞和耐热细胞敏感化。这些发现将鼓励对AAPH（或其类似物）作为温度依赖性热敏化剂进行体内评估。AAPH代表了一类新型的热敏化剂，可能有助于阐明热杀伤机制，并且可能在局部热疗中具有应用价值。
