Radiation-induced cytotoxic products

As detailed in the context of the hypoxic sensitizer discussion above, the idea that an easy-to-reduce species could function as a radiation sensitizer is not new [113-117]. Indeed, there is considerable precedent for it both in the radiation sensitization literature per se [113-115,118,125-129,132-135,138,139,142] and in classic mechanistic explanations of radiation-induced cytotoxicity [143-145]. However, as has also been made clear in the context of this earlier discourse, this idea has yet to translate into an FDA-approved XRT sensitizing product. However, as noted above, PCI-0120 (3) possesses special features that led to the consideration that it... 

Therapeutic irradiation is known to have multiple interactions with the vasculature of the irradiated tissue (12). Radiation has direct cytotoxic effects on the vascular endothelium, likely due to induction of oxidative injury. Radiation-induced injury stimulates inflammation and influx of inflammatory cells in addition to creating aprocoagulant state in the vascular space by the transcriptional induction of tissue factor with the subsequent activation of coagulation factors as well as von Willebrand factor and platelets. Experimental evidence suggests that the mechanism by which radiation initiates these responses is in part through the induction of cell-adhesion molecules including ICAM-1, E-selectin, and P-selectin and in part through local cytokine production and release (13). 

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