Methionine dietary supplementation potentiates ionizing radiation-induced gastrointestinal syndrome

Methionine is an essential amino acid needed for a variety of processes in living organisms. Ionizing radiation depletes tissue methionine concentrations and leads to the loss of DNA methylation and decreased synthesis of glutathione. In this study, we aimed to investigate the effects of methionine dietary supplementation in CBA/CaJ mice after exposure to doses ranging from 3 to 8.5 Gy of 137Cs of total body irradiation. We report that mice fed a methionine-supplemented diet (MSD; 19.5 vs. 6.5 mg/kg in a methionine-adequate diet, MAD) developed acute radiation toxicity at doses as low as 3 Gy. Partial body irradiation performed with hindlimb shielding resulted in a 50% mortality rate in MSD-fed mice exposed to 8.5 Gy, suggesting prevalence of radiation-induced gastrointestinal syndrome in the development of acute radiation toxicity. Analysis of the intestinal microbiome demonstrated shifts in the gut ecology, observed along with the development of leaky gut syndrome and bacterial translocation into the liver. Normal gut physiology impairment was facilitated by alterations in the one-carbon metabolism pathway and was exhibited as decreases in circulating citrulline levels mirrored by decreased intestinal mucosal surface area and the number of surviving crypts. In conclusion, we demonstrate that a relevant excess of methionine dietary intake exacerbates the detrimental effects of exposure to ionizing radiation in the small intestine. NEW & NOTEWORTHY Methionine supplementation, instead of an anticipated health-promoting effect, sensitizes mice to gastrointestinal radiation syndrome. Mechanistically, excess of methionine negatively affects intestinal ecology, leading to a cascade of physiological, biochemical, and molecular alterations that impair normal gut response to a clinically relevant genotoxic stressor. These findings speak toward increasing the role of registered dietitians during cancer therapy and the necessity of a solid scientific background behind the sales of dietary supplements and claims regarding their benefits.

Effects of radiotherapy on oral cavity tissues

Radiotherapy in the treatment of head and neck tumors is most often used as an independent method or in combination with surgery and / or chemotherapy. These therapeutic methods in a multidisciplinary approach generally lead to favourable therapeutic response. During radiotherapy of this region, oral mucosa is inevitably covered within irradiated volume. Radical therapy is achieved with high doses of radiation, which usually results in development of undesired toxic effects, which, depending on the time of manifestation can be acute and late. Acute radiation toxicity occurs during or immediately after completion of performed therapy, and the late one several months or years after the completed treatment. The most common acute complications in the oral cavity are inflammation of oral mucosa, loss of taste, dry mouth and secondary infections. Late complications include radiation caries, trismus, and osteoradionecrosis. The aim of this paper was to present the effects and specificities of toxicity observed on oral cavity tissues after radiotherapy.