Effects of Neutron Irradiation on PGE2 and TxB2 Levels in Biological Fluids: Modification by WR2721

摘要

Whole-body fission neutron irradiation of mice results in changes in plasma and urinary prostaglandin levels. No relationship was found between urinary TxB2 excretion and the neutron dose. Elevated plasma prostaglandin PGE2 at 2-4 days postexposure coincides with increased PGE2 in the urine. A second increase in urinary PGE2 occurred 6-10 days postirradiation, and was dose dependent up to 3.85 Gy. Plasma PGE2 levels at this time were normal. WR-2721 (a radioprotective phosphorothioate) administration markedly increased (24 hr) and then reduced (2-4 days) PGE2 excretion in nonirradiated animals. The urinary PGE2 of WR-2721-pretreated, irradiated mice paralleled those of drug-treated, nonirradiated animals for the first 5 days. However, WR-2721 injection did not modify the elevation of PGE2 occurring 6-10 days postexposure. Urinary TxB2 from nonirradiated groups was not altered by WR-2721, but the combination of drug and radiation resulted in increased levels 1-7 days postexposure. These results further implicate prostaglandins in the biological response to radiation exposure and suggest another mechanism of WR-2721 radioprotection.