Abstract:
:The mutation spectrum induced by the widely used antitumor drug cis-diamminedichloroplatinum(II) (cis-DDP) showed that cisDDP[d(ApG)] adducts, although they account for only 25% of the lesions formed, are approximately 5 times more mutagenic than the major GG adduct. We report the construction of vectors bearing a single cisDDP[d(ApG)] lesion and their use in mutagenesis experiments in Escherichia coli. The mutagenic processing of the lesion is found to depend strictly on induction of the SOS system of the bacterial host cells. In SOS-induced cells, mutation frequencies of 1-2% were detected. All these mutations are targeted to the 5' base of the adduct. Single A----T transversions are mainly observed (80%), whereas A----G transitions account for 10% of the total mutations. Tandem base-pair substitutions involving the adenine residue and the thymine residue immediately 5' to the adduct occur at a comparable frequency (10%). No selective loss of the strand bearing the platinum adduct was seen, suggesting that, in vivo, cisDDP[d(ApG)] adducts are not blocking lesions. The high mutation specificity of cisDDP[d(ApG)]-induced mutagenesis is discussed in relation to structural data.
journal_name
Proc Natl Acad Sci U S Aauthors
Burnouf D,Gauthier C,Chottard JC,Fuchs RPdoi
10.1073/pnas.87.16.6087subject
Has Abstractpub_date
1990-08-01 00:00:00pages
6087-91issue
16eissn
0027-8424issn
1091-6490journal_volume
87pub_type
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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