{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T13:53:39Z","timestamp":1772805219221,"version":"3.50.1"},"reference-count":0,"publisher":"Portland Press Ltd.","issue":"3","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1975,6,1]]},"abstract":"<jats:p>The alkylation of purine bases in DNA of several rat tissues was determined during weekly injections (10 mg\/kg) of N-[3H]methyl-N-nitrosourea, a dose schedule known to selectively induce tumours of the nervous system. Each group of animals was killed 1 week after the final injection, and the DNA hydrolysates were analysed by chromatography on Sephadex G-10. After five weekly applications, O6-methylguanine had accumulated in brain DNA to an extent which greatly exceeded that in kidney, spleen and intestine. In the liver, the final O6-methylguanine concentration was less than 1% of that in brain. Between the first and the fifth injection, the O6-methylguanine\/7-methylguanine ratio in cerebral DNA increased from 0.28 to 0.68. In addition, 3-methylguanine was found to accumulate in brain DNA whereas in the other organs no significant quantities of this base were detectable. The results are compatible with the hypothesis that O6-alkylation of guanine in DNA plays a major role in the induction of tumours by N-methyl-N-nitrosourea and related carcinogens. The kinetics of the increase of O6-methylguanine in cerebral DNA suggest that there is no major cell fraction in the brain which is capable of excising chemically methylated bases from DNA. This repair deficiency could be a determining factor in the selective induction of nervous-system tumours by N-methyl-N-nitrosourea and other neuro-oncogenic compounds.<\/jats:p>","DOI":"10.1042\/bj1480521","type":"journal-article","created":{"date-parts":[[2015,8,10]],"date-time":"2015-08-10T19:58:12Z","timestamp":1439236692000},"page":"521-525","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":162,"title":["Chemical carcinogenesis in the nervous system. Preferential accumulation of <i>O<\/i>6-methylguanine in rat brain deoxyribonucleic acid during repetitive administration of <i>N<\/i>-methyl-<i>N<\/i>-nitrosourea"],"prefix":"10.1042","volume":"148","author":[{"given":"G P","family":"Margison","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P","family":"Kleihues","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","container-title":["Biochemical Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/148\/3\/521\/564018\/bj1480521.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/148\/3\/521\/564018\/bj1480521.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,26]],"date-time":"2021-11-26T16:52:08Z","timestamp":1637945528000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/biochemj\/article\/148\/3\/521\/9931\/Chemical-carcinogenesis-in-the-nervous-system"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1975,6,1]]},"references-count":0,"journal-issue":{"issue":"3","published-print":{"date-parts":[[1975,6,1]]}},"URL":"https:\/\/doi.org\/10.1042\/bj1480521","relation":{},"ISSN":["0264-6021"],"issn-type":[{"value":"0264-6021","type":"print"}],"subject":[],"published":{"date-parts":[[1975,6,1]]}}}