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Ionizing radiation and tritium transmutation both cause formation of 5-hydroxymethyl-1-2'-deoxyuridine in cellular DNA

Journal Article · · Proc. Natl. Acad. Sci. U.S.A.; (United States)
HeLa cells grown in the presence of (methyl-/sup 3/H)thymidine contained large amounts of 5-hydroxymethyl-2'-deoxyuridine (HMdU) in their DNA. When the cells were grown in (6-/sup 3/H)thymidine and the DNA was labeled to the same specific activity, no HMdU was present. When such (6-/sup 3/H)thymidine-labeled cells were exposed to increasing amounts of ..gamma..-radiation, small but increasing amounts of HMdU were formed in their DNA. This indicates that HMdU can be formed in DNA by two distinct mechanisms. The first is the result of the transmutation of /sup 3/H to /sup 3/He (..beta.. decay) in the methyl group of thymidine, leading to formation of a carbocation. This short-lived ion reacts with hydroxide ions of water, yielding the hydroxymethyl group. HMdU that is formed by this mechanism is formed at the rate of ..beta.. decay of /sup 3/H. It appears only in (methyl-/sup 3/H)thymidine residues and is present in the DNA of both nonirradiated and ..gamma..-irradiated cells. The second mechanism is the result of the radiolysis of water caused by ionizing radiation. The resultant radical species, particularly hydroxyl radicals, may react with many sites on DNA. When the methyl group of thymine is attacked by hydroxyl radicals, the hydroxymethyl group is formed. The formation of HMdU by this mechanism was detected only when (6-/sup 3/H)thymidine-labeled cells were used, since transmutation of /sup 3/H in position 6 of thymine cannot yield HMdU. 31 references, 4 figures.
Research Organization:
New York Univ. Medical Center, NY
OSTI ID:
5931792
Journal Information:
Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 81:1; ISSN PNASA
Country of Publication:
United States
Language:
English

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