High-LET-Induced Long Lived Radicals (LLR) May Initiate Genomic Instability (TGI): Effects of Certain Antioxidants

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Watanabe, Kumagai, Miyazaki and colleagues produced strong evidence that ionizing radiations induce new kinds of long-lived radicals (LLR) with half lives of minutes to hours in cellular proteins [Rad Res 160: 95, 2003]. LLR are not lethal but are transforming, and mutagenic. They are not scavenged by DMSO but are by vitamin C, EGC and RibCys {epigallocatechin-s-O-gallate and [2(R, S)-D-ribo-1', 2', 3', 4', - Tetrahydroxybutly]-thiazolidene-4-ca riboxylic acid}, respectively}. We find that vitamin C and RibCys significantly decrease yields of CD59⁻ mutants in human-CHO hybrid A_L cells exposed to high LET carbon ion radiation [290 MeV/nucleon, LET = 100 KeV/µmeters] and alter the mutational spectrum, even when added after radiation. The principal change in spectrum is reduction in prevalence of deletions of sizes detectable at the HPRT locus (<3Mbp) and of mutants displaying TGI. Thus LLR in cellular proteins may play an important role in triggering genomic instability, an effect reducible by post treatment with certain antioxidants. Supported by: Japanese Sci. Tech Agency, NIH-NCI RO1CA82309, NASANSCORT W19133. [J Radiat Res 44:379 (2003)]