Natural Consumer Products as Candidates in Chemical Radioprotection

Abstract

This thesis examines select natural dietary compounds for their radioprotective properties in vitro. These compounds were selected on the basis of their use in the treatment of CFIDS (Chronic Fatigue Immune Dysfunction Syndrome). CFIDS in humans encompasses symptoms similar to those in ionizing radiation (IR) exposures. Therefore, compounds that address CFIDS symptoms might also have utility in dietary chemical radioprotection. Specifically, this thesis examines the radioprotective effects of plant metabolites –curcumin, andrographolide, d-limonene – and endogenous metabolites – phenylacetate, ursodeoxycholate, tauroursodeoxycholate – in clonogenic in vitro experiments. Compounds were examined for their radioprotective effects in p53 variant human colon carcinoma cells which share similar features to radiosensitive stem cells of the gastrointestinal tract. Experiments examined compounds on the basis of their chemoprotective, bystander inhibitory, radioprotective and radiomitigative properties. The d-limonene demonstrated notable chemoprotective properties as noted by the preferential toxicity to p53 defective cell lines. There were no compounds that exhibited bystander inhibitory effects. In acute high dose experiments, the phenylacetate demonstrated significant radioprotective effects up to 2 Gy with minor radioprotective effects from tauroursodeoxycholate at 0.5 Gy exposures. There were no compounds that demonstrated radiomitigative effects. Ultimately, this thesis demonstrates that natural consumer products in the treatment of IR-like syndromes provide an attractive basis on which to screen compounds the fields of radioprotection.