Single d(ApG)/cis-diamminedichloroplatinum(II) adduct-induced mutagenesis in Escherichia coli

Journal Article · Wed Aug 01 04:00:00 EDT 1990 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.87.16.6087· OSTI ID:5851472

Burnouf, D; Fuchs, R P.P. ^[1]; Gauthier, C; Chottard, J C ^[2]

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1. Institut de Biologie Moleculaire et Cellulaire de Centre National de la Recherche Scientifique, Strasbourg (France)
2. Universite Rene Descartes, Paris (France)

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 {approx}5 times more mutagenic than the major GG adduct. The authors 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{prime} base of the adduct. Single A {yields} T transversions are mainly observed (80%), whereas A {yields} G transitions account for 10% of the total mutations. Tandem base-pair substitutions involving the adenine residue and the thymine residue immediately 5{prime} 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.

• OSTI ID: 5851472
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (USA) Vol. 87:16; ISSN 0027-8424; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ADDUCTS
BACTERIA
BIOLOGICAL EFFECTS
DNA ADDUCTS
DNA BASE TRANSITIONS
ESCHERICHIA COLI
MICROORGANISMS
MUTAGENESIS
NUCLEIC ACIDS
OLIGONUCLEOTIDES
ORGANIC COMPOUNDS
PLATINUM COMPOUNDS
TRANSITION ELEMENT COMPOUNDS