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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 O4-ethyl-2'-deoxythymidine (O4-EtdThd) and O6-ethyl-2'-deoxyguanosine (O6-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 O4-EtdThd in the DNA of all organs analyzed remained stable, while O6-EtdGuo (initially formed in DNA with 3-4 times higher frequency than O4-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 O4-EtdThd content of liver DNA exceeded the O6-EtdGuo content by about a factor of 4. Since both O6-EtdGuo and O4-EtdThd are miscoding DNA lesions, the lack of enzymatic removal of O4-EtdThd is surprising in view of the apparent concern of cells to restore the integrity of the O6-position of guanine. Genetic consequences more specifically connected with the formation of O6-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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Müller et al. (1983) studied this question.
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