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Methylation products were detected in all tissues examined, the level in maternal liver being higher than in other tissues. The concentrations of 7\u2010methylguanine and 3\u2010methyladenine decreased faster in fetal than in corresponding maternal tissues, due to a higher rate of DNA synthesis in fetal tissues, as determined by incorporation of labelled thymidine. Removal of the promutagenic DNA lesion <jats:italic>O<\/jats:italic><jats:sup>6<\/jats:sup>\u2010methylguanine was most efficient in maternal and fetal liver; but it was very poorly repaired in kidney and brain. The persistence of <jats:italic>O<\/jats:italic><jats:sup>6<\/jats:sup>\u2010methylguanine relative to 7\u2010methylguanine was highest in the DNA of fetal brain. The principal targets for the transpacental carcinogenic effect of <jats:italic>N<\/jats:italic>\u2010methyl\u2010<jats:italic>N<\/jats:italic>\u2010nitrosourea under these experimental conditions were fetal neurogenic tissue and kidney; and malignant tumors developed at these sites in 31\u201034% and 15\u201016% of male and female descendants, respectively. These results support the concept that a complex interaction between DNA alkylation, repair and replication is the molecular basis of initiation of carcinogenesis by alkylating agents.<\/jats:p>","DOI":"10.1002\/ijc.2910310618","type":"journal-article","created":{"date-parts":[[2007,2,19]],"date-time":"2007-02-19T19:35:12Z","timestamp":1171913712000},"page":"779-784","source":"Crossref","is-referenced-by-count":12,"title":["Persistence of methylated purines in the dna of various rat fetal and maternal tissues and carcinogenesis in the offspring following a single transplacental dose of <i>N<\/i>\u2010methyl\u2010<i>N<\/i>\u2010nitrosourea"],"prefix":"10.1002","volume":"31","author":[{"given":"A. J.","family":"Likhachev","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V. A.","family":"Alexandrov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V. 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