“…Both 5hmU and 5hmC can be further oxidized to the corresponding 5-formyl analogues 5foU and 5foC . The enzymatic oxidation of 5hmC can also generate 5foC in DNA .…”
Section: Resultsmentioning
confidence: 99%
“…The amount of free thymine measured by this method is 9 × 10 −10 mol/g, which corresponds to approximately 0.1% of the thymine found in DNA extracted from a tissue of similar size. In rat DNA, the ratio of thymine to cytosine is approximately 1.34, 45 and the rate of spontaneous depyrimidination of thymine to cytosine is 1.28. 46 Therefore, we would have expected more thymine than cytosine in the extracts resulting from depyrimidination.…”
Section: Chemical Research In Toxicologymentioning
confidence: 99%
“…Both 5hmU and 5hmC can be further oxidized to the corresponding 5-formyl analogues 5foU and 5foC. 45 The enzymatic oxidation of 5hmC can also generate 5foC in DNA. 59 Unlike 5hmC, 5foC paired with guanine is a preferred substrate for the TDG glycosylase, 22 and 5foU is repaired by multiple members of the uracil-DNA glycosylase family.…”
Section: Chemical Research In Toxicologymentioning
The DNA of all organisms is metabolically active due to persistent endogenous DNA damage, repair, and enzyme-mediated base modification pathways important for epigenetic reprogramming and antibody diversity. The free bases released from DNA either spontaneously or by base excision repair pathways constitute DNA metabolites in living tissues. In this study, we have synthesized and characterized the stable-isotope standards for a series of pyrimidines derived from the normal DNA bases by oxidation and deamination. We have used these standards to measure free bases in small molecule extracts from rat brain. Free bases are observed in extracts, consistent with both endogenous DNA damage and 5-methylcytosine demethylation pathways. The most abundant free base observed is uracil, and the potential sources of uracil are discussed. The free bases measured in tissue extracts constitute the end product of DNA metabolism and could be used to reveal metabolic disturbances in human disease.
“…Both 5hmU and 5hmC can be further oxidized to the corresponding 5-formyl analogues 5foU and 5foC . The enzymatic oxidation of 5hmC can also generate 5foC in DNA .…”
Section: Resultsmentioning
confidence: 99%
“…The amount of free thymine measured by this method is 9 × 10 −10 mol/g, which corresponds to approximately 0.1% of the thymine found in DNA extracted from a tissue of similar size. In rat DNA, the ratio of thymine to cytosine is approximately 1.34, 45 and the rate of spontaneous depyrimidination of thymine to cytosine is 1.28. 46 Therefore, we would have expected more thymine than cytosine in the extracts resulting from depyrimidination.…”
Section: Chemical Research In Toxicologymentioning
confidence: 99%
“…Both 5hmU and 5hmC can be further oxidized to the corresponding 5-formyl analogues 5foU and 5foC. 45 The enzymatic oxidation of 5hmC can also generate 5foC in DNA. 59 Unlike 5hmC, 5foC paired with guanine is a preferred substrate for the TDG glycosylase, 22 and 5foU is repaired by multiple members of the uracil-DNA glycosylase family.…”
Section: Chemical Research In Toxicologymentioning
The DNA of all organisms is metabolically active due to persistent endogenous DNA damage, repair, and enzyme-mediated base modification pathways important for epigenetic reprogramming and antibody diversity. The free bases released from DNA either spontaneously or by base excision repair pathways constitute DNA metabolites in living tissues. In this study, we have synthesized and characterized the stable-isotope standards for a series of pyrimidines derived from the normal DNA bases by oxidation and deamination. We have used these standards to measure free bases in small molecule extracts from rat brain. Free bases are observed in extracts, consistent with both endogenous DNA damage and 5-methylcytosine demethylation pathways. The most abundant free base observed is uracil, and the potential sources of uracil are discussed. The free bases measured in tissue extracts constitute the end product of DNA metabolism and could be used to reveal metabolic disturbances in human disease.
“…U .V .-irradiation causes partial denaturation of native DNA, making accessible single-stranded regions with which CMEC can react. Thymine dimers may be one form of molecular photoproduct contributing to these denatured regions (Salganik et al 1967) . The present results at the cellular level can be interpreted in terms of such a molecular model .…”
Section: Discussionmentioning
confidence: 99%
“…In the case of DNA, the bases involved in the binding reaction appear to be guanine and thymine . Salganik, Drevich and Vasyunina (1967) showed when U .V.-irradiated native DNA is treated first with CMEC and then with pancreatic deoxyribonuclease, enzyme resistant oligonucleotides remain which appear to bind CMEC and are enriched in their content of thymine dimers . As shown in figure 1 these workers interpreted their result as indicating CMEC may bind to locally denatured regions in DNA containing dimers (TT).…”
The agent 1-cyclohexyl-3-(2-morpholinyl-4-ethyl) carbodiimide metho-ptoluene sulphonate (CMEC) has been shown to bind preferentially to U .V .-induced single-stranded regions in DNA . In our experiments mouse L cells were assayed for their colony-forming ability after U .V . -irradiation in the absence and presence of various concentrations of CMEC . U.V .-irradiated cells were more sensitive than unirradiated cells to continual exposure to CMEC . The concentration of CMEC that reduced the survival of control cells by 50 per cent, D5o, was approximately 0. 8 mg per ml, whereas the D50 for U .V.-irradiated cells was approximately 0 . 15 mg per ml . The same differential toxicity was observed by exposing cells to CMEC at a higher concentration for a shorter time immediately after U .V .-irradiation . If U.V .-irradiated cells were incubated in the absence of CMEC for approximately one generation time immediately after irradiation, the subsequent addition of the drug had no potentiating effect . In contrast CMEC did not potentiate X-ray damage to these cells . One interpretation is that CMEC reacts preferentially with U .V .-induced partiallydenatured regions in DNA and inhibits their repair and/or normal DNA replication, so that cell lethality is increased .
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