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In order to compare the kinetics of their enzymatic elimination from the DNA of liver, kidney, lung, and brain, the alkylation products O 4 -ethyl-2'-deoxythym idine (O 4 -EtdThd) and O 6 -ethyl- 2'-deoxyguanosine (O 6 -EtdGuo) were quantitated by competitive radioimmunoassay over a period of 48 h after a single pulse of the carcinogen N -ethyl-N-nitrosourea (EtNU ) applied i.p. to 10 and 28-day-old BDIX-rats. The content of O 4 -EtdThd in the DNA of all organs analyzed remained stable, while O 6 -EtdGuo (initially formed in DNA with 3 - 4 times higher frequency than O 4 -EtdThd) was rapidly removed from the DNA of liver, followed by lung and kidney, but persisted strongly in the DNA of brain. At 48 h after the EtNU -pulse, the O 4 -EtdThd content of liver DNA exceeded the O 6 -EtdGuo content by about a factor of 4. Since both O 6 -EtdG uo and O 4 -EtdThd are miscoding DNA lesions, the lack of enzymatic removal of O 4 -EtdThd is surprising in view of the apparent concern of cells to restore the integrity of the Opposition of guanine. Genetic consequences more specifically connected with the formation of O 6 -alkylguanine in DNA might be considered, e.g., possible alterations of gene expression via interference with enzymatic 5-cytosine methylation in 5'-CpG-3' sequences of newly replicated DNA

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Enzymatic Removal of O 6 -Ethylguanine versus Stability of O 4 -Ethylthymine in the DNA of Rat Tissues Exposed to the Carcinogen Ethylnitrosourea: Possible Interference of Guanine-O 6  Alkylation with 5-Cytosine Methylation in the DNA of Replicating Target Cells