Inhibition of DNA methylation in malignant MOLT F4 lymphoblasts by 6-mercaptopurine
Treatment of MOLT F4 lymphoblasts with 6-mercaptopurine (6-MP) resulted in a decrease of ATP and a depletion of S-adenosylmethionine (AdoMet). To investigate whether this might affect the methylation of DNA, we treated MOLT F4 lymphoblasts with increasing concentrations of 6-MP, followed by labeling...
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| Veröffentlicht in: | Clinical chemistry (Baltimore, Md.) Md.), 1998-03, Vol.44 (3), p.556-559 |
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| container_title | Clinical chemistry (Baltimore, Md.) |
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| creator | Lambooy, Lambert H. J Leegwater, Peter A. J van den Heuvel, Lambert P Bokkerink, Jos P De Abreu, Ronney A |
| description | Treatment of MOLT F4 lymphoblasts with 6-mercaptopurine (6-MP) resulted in a decrease of ATP and a depletion of S-adenosylmethionine (AdoMet). To investigate whether this might affect the methylation of DNA, we treated MOLT F4 lymphoblasts with increasing concentrations of 6-MP, followed by labeling with [methyl-14C]methionine and [methyl-3H]thymidine. After DNA isolation, we measured the incorporated radioactivity and determined the 14C/3H ratio as a measure for the methylation of newly formed DNA. The 14C/3H ratio was decreased by 17% with 1 mumol/L 6-MP; treatment with increasing concentrations of 6-MP up to 10 mumol/L showed a further decrease to 70%, in comparison with untreated cells. To demonstrate that the methylation of deoxycytidine residues in DNA was reduced, we quantified hydrolyzed DNA by HPLC. The 14C/3H ratio showed a decrease with increasing 6-MP concentrations, indicating that treatment with 6-MP resulted in hypomethylation of DNA. |
| doi_str_mv | 10.1093/clinchem/44.3.556 |
| format | Article |
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J ; Leegwater, Peter A. J ; van den Heuvel, Lambert P ; Bokkerink, Jos P ; De Abreu, Ronney A</creator><creatorcontrib>Lambooy, Lambert H. J ; Leegwater, Peter A. J ; van den Heuvel, Lambert P ; Bokkerink, Jos P ; De Abreu, Ronney A</creatorcontrib><description>Treatment of MOLT F4 lymphoblasts with 6-mercaptopurine (6-MP) resulted in a decrease of ATP and a depletion of S-adenosylmethionine (AdoMet). To investigate whether this might affect the methylation of DNA, we treated MOLT F4 lymphoblasts with increasing concentrations of 6-MP, followed by labeling with [methyl-14C]methionine and [methyl-3H]thymidine. After DNA isolation, we measured the incorporated radioactivity and determined the 14C/3H ratio as a measure for the methylation of newly formed DNA. The 14C/3H ratio was decreased by 17% with 1 mumol/L 6-MP; treatment with increasing concentrations of 6-MP up to 10 mumol/L showed a further decrease to 70%, in comparison with untreated cells. 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The 14C/3H ratio was decreased by 17% with 1 mumol/L 6-MP; treatment with increasing concentrations of 6-MP up to 10 mumol/L showed a further decrease to 70%, in comparison with untreated cells. To demonstrate that the methylation of deoxycytidine residues in DNA was reduced, we quantified hydrolyzed DNA by HPLC. The 14C/3H ratio showed a decrease with increasing 6-MP concentrations, indicating that treatment with 6-MP resulted in hypomethylation of DNA.</description><subject>Antineoplastic agents</subject><subject>Biological and medical sciences</subject><subject>Carbon Radioisotopes</subject><subject>DNA Methylation - drug effects</subject><subject>DNA, Neoplasm - biosynthesis</subject><subject>General aspects</subject><subject>Humans</subject><subject>Lymphocytes</subject><subject>Medical sciences</subject><subject>Mercaptopurine - pharmacology</subject><subject>Methionine - metabolism</subject><subject>Pharmacology. Drug treatments</subject><subject>Radioisotope Dilution Technique</subject><subject>Thymidine - metabolism</subject><subject>Tritium</subject><subject>Tumor Cells, Cultured</subject><issn>0009-9147</issn><issn>1530-8561</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kE9v1DAQxS0EKkvpB-CA5ANwy9aO_8Q5Vi2FSlt6oJwt2xk3Ro4T7KxW--2bdpc9jWbem_ekH0KfKFlT0rJLF0NyPQyXnK_ZWgj5Bq2oYKRSQtK3aEUIaauW8uY9-lDK32XljZJn6KwVlChJV-j3XeqDDXMYEx49vvl1hQeY-300r6eQ8GBieEomzfj-YfOIbzmO-2HqRxtNmQu2eyyrAbIz0zxO2xwSfETvvIkFLo7zHP25_f54_bPaPPy4u77aVI61aq6oU8ZzX7uGN87X0HWqBmHbThhQDoQyRlJBFbeUgZccLLW2Y5YKW4O3NTtH3w65Ux7_baHMegjFQYwmwbgtumkbTpkUi5EejC6PpWTwesphMHmvKdEvIPV_kJpzzfQCcvn5fAzf2gG608eR3KJ_OeqmOBN9NsmFcrLVtGklean-erD14anfhQy6LEDjEkr1brc71T0DtH-LlQ</recordid><startdate>19980301</startdate><enddate>19980301</enddate><creator>Lambooy, Lambert H. J</creator><creator>Leegwater, Peter A. 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Drug treatments</topic><topic>Radioisotope Dilution Technique</topic><topic>Thymidine - metabolism</topic><topic>Tritium</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lambooy, Lambert H. J</creatorcontrib><creatorcontrib>Leegwater, Peter A. 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After DNA isolation, we measured the incorporated radioactivity and determined the 14C/3H ratio as a measure for the methylation of newly formed DNA. The 14C/3H ratio was decreased by 17% with 1 mumol/L 6-MP; treatment with increasing concentrations of 6-MP up to 10 mumol/L showed a further decrease to 70%, in comparison with untreated cells. To demonstrate that the methylation of deoxycytidine residues in DNA was reduced, we quantified hydrolyzed DNA by HPLC. The 14C/3H ratio showed a decrease with increasing 6-MP concentrations, indicating that treatment with 6-MP resulted in hypomethylation of DNA.</abstract><cop>Washington, DC</cop><pub>Am Assoc Clin Chem</pub><pmid>9510861</pmid><doi>10.1093/clinchem/44.3.556</doi><tpages>4</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Clinical chemistry (Baltimore, Md.), 1998-03, Vol.44 (3), p.556-559 |
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| source | MEDLINE; Oxford University Press Journals All Titles (1996-Current) |
| subjects | Antineoplastic agents Biological and medical sciences Carbon Radioisotopes DNA Methylation - drug effects DNA, Neoplasm - biosynthesis General aspects Humans Lymphocytes Medical sciences Mercaptopurine - pharmacology Methionine - metabolism Pharmacology. Drug treatments Radioisotope Dilution Technique Thymidine - metabolism Tritium Tumor Cells, Cultured |
| title | Inhibition of DNA methylation in malignant MOLT F4 lymphoblasts by 6-mercaptopurine |
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