Office of Biological and Environmental Research

DOE Lowdose Radiation Program Workshop V

2005 Abstract

Title: Long-Term Effects of Whole-Body, High-LET Radiation on Blood Chemistry

Authors: D.S. Gridley^1,2, T. Bateman³, S.A. Hamilton³, A. Obenaus¹ and M.J. Pecaut¹

Institutions: ¹Department of Radiation Medicine, Chan Shun Pavilion Room A-1010, 1175 Campus Street, dgridley@dominion.llumc.edu; ²Department of Biochemistry & Microbiology Loma Linda University & Medical Center, Loma Linda, CA 92354 ³Bioengineering Department, Clemson University, Clemson, SC 29634

INTRODUCTION
The health consequences to astronauts exposed to high-linear energy transfer (LET) radiation during extended space missions are not yet clear. Heavy ionized nuclei, such as iron ions, could potentially pose the greatest threat. We have previously reported abnormalities in erythrocyte and leukocyte populations obtained from Sprague-Dawley rats at 9 months after exposure to ⁵⁶Fe²⁶⁺ radiation. Here we present blood chemistry data that is especially relevant to hepatic and renal function from these same animals.

MATERIALS AND METHODS
Adult male Sprague-Dawley rats (n = 32) were lightly anesthetized with isoflurane and placed into a stereotactic device at Brookhaven National Laboratory (BNL). Whole-body irradiation was performed with iron ions produced by the Alternating Gradient Synchrotron (AGS) (⁵⁶Fe, Z = 26, 5GeV/nucleon) in a single fraction at a dose rate of ~1.5 Gy/min. The animals were shipped to Loma Linda University 2 days later. At 9 months post-irradiation, blood was collected by tail vein puncture in [K₂]EDTA-coated microhematocrit tubes and centrifuged. Plasma was frozen in Microtainer® tubes (Becton Dickinson Vacutainer Systems, Franklin Lakes, NJ) until immediately before analysis utilizing the Hitachi 717 Automatic Chemistry Analyzer (Roche Diagnostics, Indianapolis, IN). Statistical analyses were performed using one-way analysis of variance (ANOVA) and Tukey’s pairwise multiple comparison test (SigmaStat^TM software, version 2.03; SPSS Inc., Chicago, IL); a P value <0.05 indicated significance.

RESULTS
Blood urea nitrogen increased with increasing dose of radiation (P<0.05); post-hoc analysis revealed that values in the 4Gy group were significantly higher than in groups receiving either 0Gy or 1Gy (P<0.01); the 2Gy group had higher values than the 1 Gy group (P<0.05), whereas a trend was noted for 2Gy vs. 0Gy (P = 0.08). Uric acid was lower in all irradiated groups (P<0.05), although post-hoc Tukey’s test indicated that only the 1Gy group differed significantly from the 0Gy group (P<0.05); for 1 Gy vs. 4Gy, p = 0.053. Aspartate aminotransferase was affected by radiation (P<0.050), with the 2Gy group having the highest level (P<0.05 vs. 1Gy). Albumin decreased with increasing radiation dose (P<0.01) and 4Gy-irradiated rats had a significantly lower level than the 1Gy animals (P<0.005); for 2Gy vs. 1Gy, p = 0.050. Glucose was significantly affected by radiation (P<0.005), with the 1Gy and 4Gy groups having lower (P<0.05) and 2Gy group having higher (P<0.005) values compared to the 0Gy control. There were no significant differences in cholesterol, triglycerides, total protein, globulin, albumin/globulin ratio, creatinine, lactate dehydrogenase, and alanine aminotransferase.

CONCLUSIONS
The data indicate that high-LET irradiation induced functional abnormalities in the kidneys, liver, and possibly other organs that were detected at 9 months post-exposure. The high blood urea nitrogen may reflect renal impairment due to decreased circulating blood volume with low renal perfusion or postrenal obstruction of urine flow. Low uric acid is associated with certain diseases including xanthinuria, a condition characterized by excretion of large amounts of xanthine, as well as xanthine kidney stones. This would be consistent with the relatively low level of uric acid found in the irradiated rats, since hypoxanthine is a precursor of uric acid. High aspartate aminotranferase is associated with necrosis of hepatocytes, myocardial cells, or skeletal muscle cells. Low albumin may indicate decreased synthesis due to liver disease or malabsorption or increased loss due to nephritic syndrome. Low glucose is associated with liver disease, adrenocortical insufficiency, and numerous other conditions including hepatoma, fibrosarcoma, and adrenal and gastric carcinomas. Thus, while we report functional changes, the mechanisms underlying the radiation response and the lack of a clear radiation dose response in some measurements will require further investigation.

Supported by NASA Coop. Agreement NCC9-79