BLOOD GLUTATHIONE AS AN INDEX OF RADIATION-INDUCED OXIDATIVE STRESS IN MICE AND HUMANS

The effect of x-rays on GSH and GSSG levels in blood was studied in mi ce and humans. An HPLC method that we recently developed was applied t o accurately determine GSSG levels in blood. The glutathione redox sta tus (GSH/GSSG) decreases after irradiation. This effect is mainly due to an increase in GSSG levels. Mice received single fraction radiother apy, at total doses of 1.0 to 7.0 Gy Changes in GSSG in mouse blood ca n be detected 10 min after irradiation and last for 6 h within a range of 2.0-7.0 Gy. The highest levels of GSSG (20.1 +/- 2.9 mu M), a 4.7- fold increase as compared with controls) in mouse blood are found 2 h after radiation exposure (5 Gy). Breast and lung cancer patients recei ved fractionated radiotherapy at total doses of 50.0 or 60.0 Gy, respe ctively. GSH/GSSG also decreases in humans in a dose-response fashion. Two reasons may explain the radiation-induced increase in blood GSSG: (a) the reaction of GSH with radiation-induced free radicals resultin g in the formation of thyl radicals that react to produce GSSG; and (b ) an increase of GSSG release from different organs (e.g., the liver) into the blood. Our results indicate that the glutathione redox ratio in blood can be used as an index of radiation-induced oxidative stress . (C) 1997 Elsevier Science Inc.