{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T11:54:39Z","timestamp":1782215679066,"version":"3.54.5"},"reference-count":0,"publisher":"Portland Press Ltd.","issue":"1","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1994,11,15]]},"abstract":"<jats:p>6-Mercaptopurine (6-MP) and methylmercaptopurine ribonucleoside (Me-MPR) are purine anti-metabolites which are both metabolized to methylthio-IMP (Me-tIMP), a strong inhibitor of purine synthesis de novo. Me-MPR is converted directly into Me-tIMP by adenosine kinase. 6-MP is converted into tIMP, and thereafter it is methylated to Me-tIMP by thiopurine methyltransferase, an S-adenosylmethionine (S-Ado-Met)-dependent conversion. S-Ado-Met is formed from methionine and ATP by methionine adenosyltransferase, and is a universal methyl donor, involved in methylation of several macromolecules, e.g. DNA and RNA. Therefore, depletion of S-Ado-Met could result in an altered methylation state of these macromolecules, thereby affecting their functionality, leading to dysregulation of cellular processes and cytotoxicity. In this study the effects of 6-MP and Me-MPR on S-Ado-Met, S-adenosylhomocysteine (S-Ado-Hcy), homocysteine and methionine concentrations are determined. Both drugs cause a decrease in intracellular S-Ado-Met concentrations and an increase in S-Ado-Hcy and methionine concentrations in Molt F4 human malignant lymphoblasts. The effects of both 6-MP and Me-MPR can be ascribed to a decreased conversion of methionine into S-Ado-Met, due to the ATP depletion induced by the inhibition of purine synthesis de novo by Me-tIMP. Both 6-MP and Me-MPR thus affect the methylation state of the cells, and this may result in dysregulation of cellular processes and may be an additional mechanism of cytotoxicity for 6-MP and Me-MPR.<\/jats:p>","DOI":"10.1042\/bj3040163","type":"journal-article","created":{"date-parts":[[2015,8,10]],"date-time":"2015-08-10T21:40:39Z","timestamp":1439242839000},"page":"163-168","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Decrease in <i>S<\/i>-adenosylmethionine synthesis by 6-mercaptopurine and methylmercaptopurine ribonucleoside in Molt F4 human malignant lymphoblasts"],"prefix":"10.1042","volume":"304","author":[{"given":"E H","family":"Stet","sequence":"first","affiliation":[{"name":"Center for Pediatric Oncology S.E. Netherlands, Department of Pediatrics, St. Radboud University Hospital of Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R A","family":"De Abreu","sequence":"additional","affiliation":[{"name":"Center for Pediatric Oncology S.E. Netherlands, Department of Pediatrics, St. Radboud University Hospital of Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J P M","family":"B\u00f6kkerink","sequence":"additional","affiliation":[{"name":"Center for Pediatric Oncology S.E. Netherlands, Department of Pediatrics, St. Radboud University Hospital of Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H J","family":"Blom","sequence":"additional","affiliation":[{"name":"Center for Pediatric Oncology S.E. Netherlands, Department of Pediatrics, St. Radboud University Hospital of Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L H J","family":"Lambooy","sequence":"additional","affiliation":[{"name":"Center for Pediatric Oncology S.E. Netherlands, Department of Pediatrics, St. Radboud University Hospital of Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T M","family":"Vogels-Mentink","sequence":"additional","affiliation":[{"name":"Center for Pediatric Oncology S.E. Netherlands, Department of Pediatrics, St. Radboud University Hospital of Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A C","family":"de Graaf-Hess","sequence":"additional","affiliation":[{"name":"Center for Pediatric Oncology S.E. Netherlands, Department of Pediatrics, St. Radboud University Hospital of Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"van Raay-Selten","sequence":"additional","affiliation":[{"name":"Center for Pediatric Oncology S.E. Netherlands, Department of Pediatrics, St. Radboud University Hospital of Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F J M","family":"Trijbels","sequence":"additional","affiliation":[{"name":"Center for Pediatric Oncology S.E. Netherlands, Department of Pediatrics, St. Radboud University Hospital of Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","container-title":["Biochemical Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/304\/1\/163\/725506\/bj3040163.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/304\/1\/163\/725506\/bj3040163.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,24]],"date-time":"2021-11-24T00:55:17Z","timestamp":1637715317000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/biochemj\/article\/304\/1\/163\/36632\/Decrease-in-S-adenosylmethionine-synthesis-by-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1994,11,15]]},"references-count":0,"journal-issue":{"issue":"1","published-print":{"date-parts":[[1994,11,15]]}},"URL":"https:\/\/doi.org\/10.1042\/bj3040163","relation":{},"ISSN":["0264-6021","1470-8728"],"issn-type":[{"value":"0264-6021","type":"print"},{"value":"1470-8728","type":"electronic"}],"subject":[],"published":{"date-parts":[[1994,11,15]]}}}