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Normal human repair\u2010proficient fibroblasts and <jats:italic>cis<\/jats:italic>\u2010DDP repair\u2010deficient xeroderma pigmentosum (XP) cells were used as host cells to study the effect of <jats:italic>cis<\/jats:italic>\u2010DDP on the inhibition of shuttle vector replication and mutagenesis. Transfection of <jats:italic>cis<\/jats:italic>\u2010DDP\u2010treated pZ189 into normal and XP cell lines resulted in a marked increase in the mutation frequency and a decrease in the replication efficiency of the vector. However, these effects were much greater for the plasmid propagated in XP cells. Atomic absorption spectroscopy showed that six to eight Pt\u2010DNA adducts per plasmid were necessary to inhibit plasmid replication by 50% in normal cells. In contrast, only one to two Pt\u2010DNA adducts were necessary to inhibit replication of the plasmid by 50% in XP cells. Analysis of mutation sites demonstrated that <jats:italic>cis<\/jats:italic>\u2010DDP treatment resulted primarily in single and double mutations separated by one base and limited to a few locations within the 85\u2010bp mature tRNA. Propagation of the <jats:italic>cis<\/jats:italic>\u2010DDP\u2010treated vector in either normal or XP cells led to predominantly transversion mutations at AGA, AGG, and GAG sites and a <jats:italic>cis<\/jats:italic>\u2010DDP\u2010associated deletion of 174 bp. Although mutations occurred at target sites for <jats:italic>cis<\/jats:italic>\u2010DDP adduct formation, there was no correlation between sites of mutation and the most frequent sites of adduct formation.<\/jats:p>","DOI":"10.1002\/mc.2940040512","type":"journal-article","created":{"date-parts":[[2007,2,21]],"date-time":"2007-02-21T20:15:31Z","timestamp":1172088931000},"page":"397-406","source":"Crossref","is-referenced-by-count":30,"title":["Spectrum of <i>cis<\/i>\u2010diamminedichloroplatinum(II)\u2010induced mutations in a shuttle vector propagated in human cells"],"prefix":"10.1002","volume":"4","author":[{"given":"Glenn J.","family":"Bubley","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian P.","family":"Ashburner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beverly 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