Spectrum of cisplatin-induced mutations in Escherichia coli

Journal Article · Mon Jun 01 04:00:00 EDT 1987 · Proc. Natl. Acad. Sci. U.S.A.; (United States)

DOI:https://doi.org/10.1073/pnas.84.11.3758· OSTI ID:6327901

Burnouf, D; Duane, M; Fuchs, R P

Using a forward-mutation assay based on the inactivation of the tetracycline-resistance gene located on plasmid pBR322, we have determined the mutation spectrum induced in Escherichia coli by cisplatin (cis-diamminedichloroplatinum(II)), a widely used antitumor drug. Cisplatin is known to form mainly intrastrand diadducts at ApG and GpG sites. We found that cisplatin efficiently induces mutations in an SOS-dependent way (i.e., dependent upon UV irradiation of the host bacteria). More than 90% of the mutations are single-base-pair substitutions occurring at the potential sites of cisplatin adducts (ApG and GpG). Taking into account the relative proportions of ApG and GpG adducts, we found that the ApG adducts are at least 5 times more mutagenic than the GpG adducts. Moreover, a strong mutation specificity was seen at the 5' side of the ApG adducts (A X T----T X A transversions). The observation that most mutations occur at the 5' end of the adduct at both ApG and GpG sites is discussed in relation to recent structural data.

• Research Organization: Institut de Biologie Moleculaire et Cellulaire du Centre National de la Recherche Scientifique, Strasbourg, France
• OSTI ID: 6327901
• Journal Information: Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 11; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

560130* -- Radiation Effects on Microorganisms
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ADDUCTS
ANTINEOPLASTIC DRUGS
BACTERIA
DNA ADDUCTS
DRUGS
ELECTROMAGNETIC RADIATION
ESCHERICHIA COLI
GENES
MICROORGANISMS
MUTAGENESIS
MUTAGENS
MUTATIONS
RADIATIONS
ULTRAVIOLET RADIATION