US EPA

6868872 

Journal Article 

Misreading of DNA templates containing 8-hydroxydeoxyguanosine at the modified base and at adjacent residues 

Kuchino, Y; Mori, F; Kasai, H; Inoue, H; Iwai, S; Miura, K; Ohtsuka, E; Nishimura, S 

1987 

1 

Nature
ISSN: 0028-0836
EISSN: 1476-4687 

MACMILLAN MAGAZINES LTD 

LONDON 

327 

6117 

77-79 

English 

3574469 

10.1038/327077a0 

WOS:A1987H172600060 

It has been shown previously that deoxyguanosine residues in DNA are hydroxylated at the C-8 position both in vitro and in vivo to produce 8-hydroxydeoxyguanosine (8-OH-dG) by various agents that produce oxygen radicals such as reducing reagents-O2, metal ions-O2, polyphenol-H2O2-Fe3+, asbestos-H2O2 or ionizing radiation. These agents are mostly either mutagenic or carcinogenic; therefore, the formation of 8-OH-dG can also be considered a likely cause of mutation or carcinogenesis by oxygen radicals. It is of interest to know whether the 8-OH-dG residue in DNA is misread during DNA replication. To answer this question, we have examined the effect of the 8-OH-dG residue in DNA on the fidelity of DNA replication using a DNA synthesis system in vitro with Escherichia coli DNA polymerase I (Klenow fragment). The synthetic oligodeoxynucleotides, with or without an 8-OH-dG residue in a specified position, were chemically synthesized and used as templates for DNA synthesis under the conditions of the dideoxy chain termination sequencing method. Surprisingly, in addition to misreading of the 8-OH-dG residue itself, pyrimidines next to the 8-OH-dG residue (G has not yet been tested) were also misread. 

Environmental Studies; 8-hydroxy-2'-deoxyguanosine; Free Radicals; Deoxyguanosine; Medical research; Genetics; Deoxyribonucleic acid; Deoxyguanosine -- genetics; DNA -- drug effects; Base Sequence; DNA Replication; DNA Damage; Oxygen -- pharmacology; Deoxyguanosine -- analogs & derivatives; Templates, Genetic; DNA -- genetics; Mutation