Thiol-induced biochemical modification of chemo- and radioresponses.

There is considerable interest in the role of thiols and redox enzymes as modulators of chemo- and radioresponses from both therapeutic and theoretical perspectives. The metabolism of GSH and the functioning of the GSH redox cycle can have a significant impact on the response of cells to both chemical and radiation stresses. From this rapidly developing research area, attention has been focused on recent progress in several areas: the use of GSH-depletion to reverse chemo-induced resistance to further chemical treatment; the significance of GSH transferase activity in chemoresistant cells; the effectiveness of GSH-depletion in sensitizing radioresistant cells; and the evidence for an alternative GSH-linked recovery pathway. From an examination of these areas, it seems warranted to conclude the following: First, manipulation of the redox state is effective in enhancing the cytotoxic effect of radiation and some chemotherapeutic agents in radio- and chemoresistant cells; second, additional possibilities for a therapeutic advantage may be gained as new redox modifiers are developed; and last, membrane domains may provide important sites for redox alterations by naturally occurring substrates or by drugs specifically designed to alter this interaction.