Lenarczyk, M., Ueno, A., Vannais, D. B., Kraemer, S., Kronenberg, A., Roberts, J. C., Tatsumi, K., Hei, T. K. and Waldren, C. A. The “Pro-drug” RibCys Decreases the Mutagenicity of High-LET Radiation in Cultured Mammalian Cells. Radiat. Res. 160, 579–583 (2003). We are carrying out studies aimed at reducing the mutagenic effects of high-LET 56 Fe ions and 12 C ions ( 56 Fe ions, 143 keV/μm; 12 C ions, 100 keV/μm) with certain drugs, including RibCys [2-( R,S )- d -ribo-(1′,2′,3′,4′-tetrahydroxybutyl)-thiazolidine-4( R )-carboxylic acid]. RibCys, formed by condensation of l -cysteine with d -ribose, is designed so that the sulfhydryl amino acid l -cysteine is released intracellularly through nonenzymatic ring opening and hydrolysis leading to increased levels of glutathione (GSH). RibCys (4 or 10 m M ), which was present during irradiation and for a few hours after, significantly decreased the yield of CD59 − mutants induced by radiation in A L human–hamster hybrid cells. RibCys did not affect the clonogenic survival of irradiated cells, nor was it mutagenic itself. These results, together with the minimal side effects reported in mice and pigs, indicate that RibCys may be useful, perhaps even when used prophylactically, in reducing the mutation load created by high-LET radiation in astronauts or other exposed individuals.