期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1982
卷号：79
期号：3
页码：744-748
DOI：10.1073/pnas.79.3.744
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Snake venom phosphodiesterase or endonuclease S1 digestion of neocarzinostatin chromophore-treated DNA, labeled in its thymidine residues, liberates an unusual labeled nucleoside from the 5' end of a drug-induced break. This substance, isolated by reverse-phase HPLC, possesses carbons from both the thymine and the deoxyribose moieties of thymidine in the DNA but, unlike thymidine, is readily degraded at pH 12 to thymine and a sugar fragment. The altered nucleoside was shown to contain a carbonyl group by its reduction with NaBH4 to form a substance that has the chromatographic properties of thymidine and by its reaction with various hydrazines to form the respective hydrazone derivatives; the carbonyl exists as the 5' aldehyde as shown by its mild chemical oxidation to the carboxylic acid with simultaneous loss of the 5' 3H. Mass spectral analysis showed a fragmentation pattern compatible with the structure thymidine-5'-aldehyde. These data indicate that the nonprotein chromophore of neocarzinostatin, in the presence of a reducing substance (2-mercaptoethanol) and molecular oxygen, selectively oxidizes the 5' carbon of nucleosides in DNA to the aldehyde, resulting in a strand break and a DNA fragment bearing nucleoside-5'-aldehyde at its 5' end.
