Short-term systemic effects of head and neck irradiation

Various localized side effects which accompany head and neck irradiation [IR] have been widely reported. However, systemic side effects/have been only sparsely reported in the short-term period post-IR in an animal model. The potential modulatory role of zinc-desferrioxamine [Zn-DFO] on IR effects was examined because of its known ability to protect against the damage induced by free radicals which are mediated by redox-active metal ions.

We used three groups of male Wistar rats: a] sham irradiated controls b] irradiated [15 Gy]; c] irradiated and treated with Zn-DFO [20 mg/k] one hour prior to IR. During the first two weeks post-IR, body weight and food and water intake were monitored daily, while lymphocytes, segmented neutrophils and white blood cells [WBC] were counted at 10 minutes 4 and 16 hours and 1, 3, 7 and 14 days. Serum TNF-a and IL-6 were obtained at 10 minutes and 7 days.

On day 7 post-IR, body weight and food and water intake were reduced by 84% 96% and 85% [p < 0.01], respectively in the above mentioned three groups of rats. This resulted in the death of 22% of the animals and was followed by recovery towards the end of the second week. At all time points examined between 10 minutes and 14 days, WBC were reduced by 52-74%. On the 7th day, Zn-DFO demonstrated a 33% protective effect against the WBC reduction. At 10 mins post-IR, a 84.8-fold [p < 0.01] increase of TNF-alpha, but not IL-6, was noted. However, on the 7th day post-IR, both TNF-alpha and IL-6 levels were increased by 48.5-fold and 102.5-fold [0.01], respectively.

The data presented delineate the severe short-term systemic effects of head and neck IR in a rat model. We suggest considering the severe cachectic and immunocompromised status of the animals when performing various short-term studies with this model. During this period nutritional and immunological support for the examined animals is recommended. Further evaluation of the underlying mechanisms of IR-induced leukopenia and cachexia in animals and the possible implications for humans is warranted.