Platinum(II) complexes generate frame-shift mutations in test strains of Salmonella typhimurium

Andersen, Kirsten S.

doi:10.1016/0165-1218(79)90014-4

Cited by 52 publications

(11 citation statements)

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“…The molecular nature of cisplatin-induced mutations was previously investigated by using either the histidine reversion assays in Salmonella typhimurium (16)(17)(18)(19)(20)48) or the lacI forward-mutation assay in E. coli (14). From the reversion assays in S. typhimurium, it was concluded that cisplatin was able to revert base-pair-substitution strains, provided plasmid pKM101 was present, but not frameshiftmutation strains (48).…”

Section: Comparison Of Our Mutation Data With the Other Availablementioning

confidence: 99%

“…It was also found to be mutagenic in E. coli (14,15) and Salmonella typhimurium (16)(17)(18)(19)(20) and carcinogenic in mouse and rat (19,20). The contribution of the different DNA adducts to the mutagenic potency is largely unknown.…”

mentioning

confidence: 99%

“…Of the substitution mutations, 18 (75%) represent transversions and -6 (25%) represent transitions. Among the 18 transversions, 12 are A T--T A transversions, 5 are G-C-+TA transversions, and 1 is a G*C--C*G transversion (Table 2). The relative proportions of the transition mutations are given in Table 2.…”

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confidence: 99%

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Spectrum of cisplatin-induced mutations in Escherichia coli.

Burnouf¹,

Duane²,

Fuchs³

1987

Proc. Natl. Acad. Sci. U.S.A.

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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-diamminedichlo-roplatinum(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 ofthe ApG adducts (A'T-+T-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.Cisplatin [cis-diamminedichloroplatinum(II)] is widely used in the treatment of some human tumors, such as head and neck, ovarian, and testicular cancers (1). Cisplatin preferentially forms intrastrand adducts between the N-7 atoms of adjacent purines (2, 3).Recently, several studies (4-10) focused on the characterization and quantification of the different adducts that form when cisplatin or cis-(1,2-cyclohexanediamine)dichloroplatinum(II) reacts with DNA or model oligonucleotides. As a result, at the lowest levels of modification that could be analyzed with cisplatin (in the range of 0.002 to 0.01 Pt adducts per nucleotide), 65% of the adducts were found to be at GpG sequences and 25% at ApG sequences, whereas GpNpG adducts could represent 6% (6).In Escherichia coli, cisplatin was shown to cause filamentation (11), the induction of RecA protein synthesis (12), and the induction of prophage X (13). It was also found to be mutagenic in E. coli (14,15) and Salmonella typhimurium (16)(17)(18)(19)(20) and carcinogenic in mouse and rat (19,20). The contribution of the different DNA adducts to the mutagenic potency is largely unknown. From results obtained with the lacd system developed by , Brouwer et al. (14) concluded that GpApG and GpCpG sequences are hot spots for cisplatin-induced base-substitution mutations.In this paper, we present the analysis of cisplatin-induced mutations by a forward-mutation assay-namely, the inactivation of the tetracycline-resistance gene located on plasmid pBR322 (24). This assay was previously shown to respond to the different classes of mutations (25,26). MATERIALS AND METHODSStrains, Plasmids, and Culture Medium. Strains AB1186 (uvrA) and GW2100 (umuC122) and the corresponding wildtype strain AB1157 were used (27,28). pBR322 plasmid DNA was grown in AB1157 and purified as described (24). Rich Luria-Bertani (LB) medium contained ampicillin (50 ,g/ml) or tetracycline (20 ,ug/ml).In Vitro Reaction of Cisplatin with Plasmid DNA. Reaction of supercoiled pBR322 DNA w...

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Section: Comparison Of Our Mutation Data With the Other Availablementioning

confidence: 99%

mentioning

confidence: 99%

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Spectrum of cisplatin-induced mutations in Escherichia coli.

Burnouf¹,

Duane²,

Fuchs³

1987

Proc. Natl. Acad. Sci. U.S.A.

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“…The antineoplastic compound cis-diamminedichloroplatinum (11) (cis-DDP) has been shown t o be mutagenic in bacterial test systems [Andersen, 1979;Beck and Brubaker, 1975;I3eck and Fisch, 1980; Benedict e t al, 1977; Lecointe e t al, 1977;Monti-Bragadin et al, 19751 and t o Chinese hamster V79 cells [Zwelling et al, 19791. Several investigators testing various chemical compounds in mutagenicity assays believe chemical impurities which were present in the compounds or the resulting breakdown products were responsible for positive mutagenic activity [Kramers, 1975;Marnett and Tuttle, 1980;Mulcai and Goldstein, 1976;Nestmann et al, 1979;Shamberger e t al, 1974;Shamberger et al, 1979;Stoltz et al, 19771 and when these impurities were removed from the parent compound, the mutagenic effect was shown to be less or completely absent.…”

Section: Introductionmentioning

confidence: 99%

The mutagenic effect of cis‐diamminedichloroplatinum (II) and its degradation products in the ames microbial assay

Peer¹,

Litz²

1981

Environ. mutagen

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cis-Diamminedichloroplatinum (II), an antitumor compound which exhibits mutagenic activity, and its degradation products platin B salt, magnus red, and magnus red anion salt were tested in the Ames microbial mutagenicity assay. The purpose of this investigation was to determine if the positive mutagenic response of the platinum compound could be due to, or enhanced by, the presence of degradation products. Results indicate that platinum degradation complexes are weak mutagens which are capable of inducing both base pair and frameshift-type mutations.

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“…Using the rec assay, Nakamuro et al (23) tested five selenium compounds (35) The role of platinum compounds as cancer chemotherapeutic agents has resulted in several investigations on the capacity of these compounds to act as bacterial mutagens (37)(38)(39)(40). In particular, the stereospecificity implicit in the usefulness of cis-platinum (II) diamminedichloride (cis-PDD) as compared to its transisomer in chemotherapy has also been examined in in vitro bioassays.…”

Section: Effects Of Metals In Bacterial Bioassaysmentioning

confidence: 99%

Effects of metals in in vitro bioassays.

Sirover¹

1981

Environ Health Perspect

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The capacity of in vitro bioassays to detect the potential carcinogenicity of metal compounds is reviewed. The in vitro bioassays discussed include: bacterial reversion analysis to determine the capacity of metal salts to revert SalmoneUa typhimurium histidine auxotrophs or to revert Escherichia coli WP 2 tryp-to tryptophan prototrophy; examination of the ability of metal salts to preferentially inhibit cell growth in Bacillus subtilis cells deficient in DNA repair pathways; determination of the ability of metal salts to induce resistance to base analogs in mammalian cells; the capacity of metal salts to enhance viral transformation of mammalian cells or to transform cells in the absence of virus; and the ability of metal salts to induce chromosomal aberrations in mammalian cells. Using each of these in vitro bioassays, diverse metal compounds have been identified as potential carcinogens. Furthermore, the use of different compounds of a specific metal may allow a determination of the valence which may be required for carcinogenesis.

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Platinum(II) complexes generate frame-shift mutations in test strains of Salmonella typhimurium

Cited by 52 publications

References 5 publications

Spectrum of cisplatin-induced mutations in Escherichia coli.

Spectrum of cisplatin-induced mutations in Escherichia coli.

The mutagenic effect of cis‐diamminedichloroplatinum (II) and its degradation products in the ames microbial assay

Effects of metals in in vitro bioassays.

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