The role of thiols in lethal and mutational radiation damage

Over the last few decades, free radicals have been increasingly implicated in biological processes including radiation effects, ageing, carcinogenesis, initiation and progression of various diseases, toxicity of chemicals and drugs. In this field Radiation Biology has played an important role in the development of both technical and cultural background, because it was very soon recognized the radical nature of processes following exposure to ionizing radiation. Several studies have pointed out the importance of both radicals, reacting with cellular targets, and endogenous thiols, mainly represented by glutathione, in controlling radiation responses of living cells. Experimental supports for such a role mainly rest on observations made on cell lines depleted of glutathione content because of a genetic defect or as result of a pharmacological manipulation. We present a study on the influence of endogenous and exogenous thiols on the correlation between lethal and mutational damage in mammalian cells. Survival (S) and induction of HPRT- mutation (M) were measured in cells irradiated with X-rays either after treatment with BSO or in the presence of MEA or GSH. In control experiments log of S is linearly correlated to M. Incubation with 1 mM BSO reduces cellular GSH content and produces an increase in radiosensitivity with regard to both lethal and mutagenic effects. In the presence of MEA a concentration dependent radioprotective effect can be observed on both end-points. GSH added to cells immediately or 90 min before irradiation only displays a slight protective effect on lethality. The yield of mutant cells is not significantly affected when GSH is added immediately before irradiation.(ABSTRACT TRUNCATED AT 250 WORDS)