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Total body exposure to ionizing radiations results in widespread cellular damage which is manifest by the promptly ensuing “toxemia” known as radiation illness. The cellular damage has in the past been considered largely due to (a) protein denaturation and (b) the formation of “toxic products.” These concepts resulted in various forms of symptomatic and replacement therapy for radiation illness. Recent reports have stimulated new investigative and therapeutic endeavor in this field by calling attention to the effects produced by the ionization products of irradiated water on the sulfhydryl enzyme systems. These ionization products of irradiated water (OH, O2H and H2O2, etc.) (1, 2) are active oxidizing agents and have been shown to inhibit the sulfhydryl-containing enzymes (3–6), the degree of inhibition being directly related to the dosage of radiation. High doses of radiation produce irreversible enzymatic inhibition presumably by protein denaturation, whereas the inhibition from low doses may be reversed by the addition of glutathione (3–7). In fact, Shirai (8) has reported beneficial effects following glutathione treatment of 32 patients who were known to be suffering from roentgen intoxication as a result of x-ray therapy for uterine carcinoma. As a result of these observations, it was considered desirable to study the effect of glutathione and other sulfhydryl-containing compounds on the course of radiation illness. The other —SH compounds considered for this study were dithiopropanol (BAL) and cysteine. BAL contains more sulfhydryl per mole than the other agents but is extremely toxic. Cysteine and glutathione are relatively nontoxic. Glutathione was selected for the initial experiments, in preference to cysteine, for the following reasons: Mammalian tissues all contain appreciable amounts of glutathione but only small amounts of free cysteine or cystine, indicating that the organism makes some effort to keep glutathione intact. There is also evidence that glutathione may be less affected than cysteine by the action of certain enzymes present in tissues. For example, one enzyme, “cysteine disulfhydrase,” is known to produce H2S from cysteine, but not from glutathione (9). In addition, the role of glutathione in enzymatic reactivation (10, 11, 12) and cellular metabolism (7, 10, 13–16) further suggested its selection. Barron and Singer (17, 18) showed that a large number of enzymes need the —SH group in order to catalyze the metabolism of fats, carbohydrates, and proteins. They suggested that the action of glutathione in cellular systems was that of continuous reactivation of these —SH enzymes. Voegtlin (13) suggested that the reducing action of glutathione would maintain the activity of the enzymes that catalyze protein synthesis and thereby favorably influence growth. Voegtlin and Chalkley (19) both reported that glutathione accelerates nuclear growth and mitosis.