Low folate status increases chromosomal damage by X-ray irradiation

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Abstract
Purpose: To examine how folate status influences chromosomal damage following X-ray irradiation. Material and methods: In an animal study, mice were fed either a low, basal, or high folic acid diet (0, 2, or 40 mg/kg diet, respectively) for 4 weeks, and then given total body irradiation (TBI) at 0.5 Gy. In a human study, subjects were supplemented with folic acid (800 μg/day) for 2 weeks and their peripheral blood was irradiated at 0.5 Gy in vitro. Chromosomal damage was determined by micronucleus assay. Results: In an animal study, TBI-induced chromosomal damage was higher and folate concentration was lower in the bone marrow of the low folic acid group compared to the other two diet groups. The chromosomal damage and folate concentration were comparable between the basal and high folic acid groups. TBI administered to mice decreased folate in the plasma, erythrocyte and bone marrow. In a human study, supplementation with folic acid increased plasma folate, but did not influence either plasma homocysteine or X-ray-induced chromosomal damage in lymphocytes. Conclusion: Low folate status increases susceptibility to X-ray-induced chromosomal damage, but excessive folic acid supplementation under normal conditions yields no further protection due to folate saturation in the target tissue.