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Modulation of Radiation-Induced Apoptosis by ThiolaminesExposure to the thiolamine radioprotector N-(2-mercaptoethyl)-1,3-propanediamine (WR-1065) induced apoptosis in the mouse TB8-3 hybridoma after 60-minute (LD(sub50) = 4.5mM) or during a 20-hour (LD(sub50) = 0.15 mM) exposure. In contrast, a 20-hour exposure to 17 mM L-cysteine or 10 mM cysteamine was required to induce 50 percent apoptosis within 20 hours. Apoptosis was not induced by either a 60-minute or 20-hour exposure to 10 mM of the thiazolidime prodrugs ribose-cysteine (RibCys) or ribose-cysteamine (RibCyst). Thiolamine-induced apoptosis appeared to be a p53-independent process since it was induced by WR-1065 exposure in human HL60 cells. Exposure to WR-1065 (4mM for 15 minutes) or cysteine (10mM for 60 minutes) before and during irradiation protected cells against the induction of both DNA double-strand breaks and apoptosis, while exposure to RibCys (10 mM for 3 hours) did not. Treatment with either WR-1065, cysteine, RibCys or RibCyst for 60 minutes beginning 60 minutes after irradiation did not affect the level of radiation-induced apoptosis. In contrast, treatment with either cysteine, cysteamine or RibCys for 20 hours beginning 60 minutes after irradiation enhanced radiation-induced apoptosis. Similar experiments could not be conducted with WR-1065 because of its extreme toxicity. Our results indicate that thiolamine enhancement of radiation-induced apoptosis is not involved in their previously reported capacity to reduce radiation-induced mutations.
Document ID
20000112938
Acquisition Source
Headquarters
Document Type
Reprint (Version printed in journal)
External Source(s)
Authors
Warters, R. L.
(Utah Univ. Salt Lake City, UT United States)
Roberts, J. C.
(Utah Univ. Salt Lake City, UT United States)
Wilmore, B. H.
(Utah Univ. Salt Lake City, UT United States)
Kelley, L. L.
(Utah Univ. Salt Lake City, UT United States)
Date Acquired
August 19, 2013
Publication Date
January 1, 1997
Publication Information
Publication: International Journal of Radiation Biology
Volume: 72
Issue: 4
ISSN: 0955-3002
Subject Category
Life Sciences (General)
Funding Number(s)
CONTRACT_GRANT: NAGW-4914
CONTRACT_GRANT: NIH-5R29GM44785
CONTRACT_GRANT: 5P30-CA42401
Distribution Limits
Public
Copyright
Other

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