Elucidating the role of transiently hypoxic tumour cells on radiation resistance

Abstract

The link between hypoxic conditions and radiation sensitivity is well-established, however the dynamic nature of hypoxia is often overlooked. The contribution of acute/transient hypoxia versus chronic conditions to radiosensitivity has been investigated by Wadsworth et al. using two hypoxia markers and pentoxifylline to increase blood flow to regions of transient hypoxia.

Fig. 1. Distinguishing transient and chronic hypoxia in vivo using EF5, Pimonidazole and pentoxifylline.

In each schematic the relative timing of administration of the drugs are indicated. a EF5 and Pimonidazole (Pimo) were co-administered and identified the hypoxic fraction, which was almost exclusively positive for both hypoxia markers. b In contrast, when the administration of the two markers was separated by 72 h there was little co-staining and an evident Pimo positive necrotic population. c The interval between administration of the hypoxia markers was reduced to 24 h, here co-stained hypoxic and necrotic cells were evident as well as an EF5 only population. d When the conditions shown in (c) were repeated with the inclusion of pentoxifylline (pent) to increase blood flow and reoxygenate transiently hypoxic cells prior to Pimo or EF5 injection, the remaining Pimo and EF5 labelled cells represented chronically hypoxic cells.