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The 'Pro-Drug' RibCys Decreases The Mutagenicity of High LET Radiation in Cultured Mammalian CellsWe have initiated studies aimed at reducing the mutational effects of high LET radiation such as Fe-56 ions and C-12 ions with certain drugs. The mutagenicity of high LET (143 keV/micrometer) Fe-56 or C-12 ions (LET = 100 keV/micrometer) was quantified at the CD59 locus of human-hamster hybrid AL cells. RibCys [2,S)-D-ribo-(1',2',3',4'- Tetrahydroxybutyl)-thiazolidine-4(R)-ca riboxylic acid], formed by condensation of L-cysteine with D-ribose, is designed so that the sulfhydryl amino acid L-cysteine is released intracellularly via nonenzymatic ring opening and hydrolysis leading to increased levels of glutathione (GSH). RibCys (4 or 10 mM), present during irradiation and a few hours post-irradiation, significantly decreased the yield of CD59(-) mutants induced by radiation. 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 load of mutations created by high LET radiation in astronauts or other exposed individuals. RibCys is an attractive drug that may reduce the risk of carcinogenesis in people exposed to high LET radiation.
Document ID
20000109818
Acquisition Source
Goddard Space Flight Center
Document Type
Reprint (Version printed in journal)
Authors
Lenarczyk, M.
(Colorado State Univ. Fort Collins, CO United States)
Ueno, A.
(Colorado State Univ. Fort Collins, CO United States)
Vannais, D. B.
(Colorado State Univ. Fort Collins, CO United States)
Kraemer, S.
(Colorado State Univ. Fort Collins, CO United States)
Kronenberg, A.
(California Univ., Lawrence Berkeley Lab. Berkeley, CA United States)
Roberts, J. C.
(Utah Univ. Salt Lake City, UT United States)
Tatsumi, K.
(National Inst. of Radiological Sciences Chiba, Japan)
Hei, T. K.
(Columbia Univ. New York, NY United States)
Waldren, C. A.
(Colorado State Univ. Fort Collins, CO United States)
Date Acquired
August 19, 2013
Publication Date
January 1, 2000
Subject Category
Life Sciences (General)
Report/Patent Number
COSPAR Paper F2.1-0012
Funding Number(s)
CONTRACT_GRANT: NIH-5-R29-GM-44785
CONTRACT_GRANT: NIH-NCI-75384
CONTRACT_GRANT: DOE-522507
CONTRACT_GRANT: CA42401
CONTRACT_GRANT: NIH-NCI-36447
CONTRACT_GRANT: NAGW5-3768
CONTRACT_GRANT: NASA Order W-19133
Distribution Limits
Public
Copyright
Other

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