MersV1, Main, Exploration, bibRecord, 004028

Mutagenic and genotoxic effects of DNA adducts formed by the anticancer drug cis-diamminedichloroplatinum(II).

Identifieur interne : 004028 ( Main/Exploration ); précédent : 004027; suivant : 004029

Mutagenic and genotoxic effects of DNA adducts formed by the anticancer drug cis-diamminedichloroplatinum(II).

Auteurs : K J Yarema [États-Unis] ; S J Lippard ; J M Essigmann

Source :

Nucleic acids research [ 0305-1048 ] ; 1995.

RBID : pubmed:7479066

Descripteurs français

KwdFr :
- Adduits à l'ADN (toxicité), Altération de l'ADN (génétique), Bactériophage M13 (génétique), Cisplatine (toxicité), Données de séquences moléculaires, Escherichia coli (), Escherichia coli (génétique), Mutagènes (toxicité), Mutation ponctuelle, Séquence nucléotidique, Tests de mutagénicité.
MESH :
- génétique : Altération de l'ADN, Bactériophage M13, Escherichia coli.
- toxicité : Adduits à l'ADN, Cisplatine, Mutagènes.
- Données de séquences moléculaires, Escherichia coli, Mutation ponctuelle, Séquence nucléotidique, Tests de mutagénicité.

English descriptors

KwdEn :
- Bacteriophage M13 (genetics), Base Sequence, Cisplatin (toxicity), DNA Adducts (toxicity), DNA Damage (genetics), Escherichia coli (drug effects), Escherichia coli (genetics), Molecular Sequence Data, Mutagenicity Tests, Mutagens (toxicity), Point Mutation, SOS Response, Genetics.
MESH :
- chemical , toxicity : Cisplatin, DNA Adducts, Mutagens.
- drug effects : Escherichia coli.
- genetics : Bacteriophage M13, DNA Damage, Escherichia coli.
- Base Sequence, Molecular Sequence Data, Mutagenicity Tests, Point Mutation, SOS Response, Genetics.

Abstract

The toxicity and mutagenicity of three DNA adducts formed by the anticancer drug cis-diamminedichloroplatinum(II) (cis-DDP or cisplatin) were investigated in Escherichia coli. The adducts studied were cis-[Pt(NH3)2(d(GpG))] (G*G*), cis-[Pt(NH3)2(d(ApG))] (A*G*) and cis-[Pt(NH3)2(d(GpTpG))] (G*TG*), which collectively represent approximately 95% of the DNA adducts reported to form when the drug damages DNA. Oligonucleotide 24-mers containing each adduct were positioned at a known site within the viral strand of single stranded M13mp7L2 bacteriophage DNA. Following transfection into E. coli DL7 cells, the genomes containing the G*G*, A*G* and G*TG* adducts had survival levels of 5.2 +/- 1.2, 22 +/- 2.6 and 14 +/- 2.5% respectively, compared to unmodified genomes. Upon SOS induction, the survival of genomes containing the G*G* and A*G* adducts increased to 31 +/- 5.4 and 32 +/- 4.9% respectively. Survival of the genome containing the G*TG* adduct did not increase upon SOS induction. In SOS induced cells, the G*G* and A*G* adducts gave rise predominantly to G-->T and A-->T transversions respectively, targeted to the 5' modified base. In addition, A-->G transitions were detected for the A*G* adduct and low levels of tandem mutations at the 5' modified base as well as the adjacent 5' base were also observed for both adducts. The A*G* adduct was more mutagenic than the G*G* adduct, with a mutation frequency of 6% compared to 1.4% for the latter adduct. No cis-[Pt(NH3)2)2+ intrastrand crosslink-specific mutations were observed for the G*TG* adduct.

DOI: 10.1093/nar/23.20.4066
PubMed: 7479066

Affiliations:

États-Unis

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<front><div type="abstract" xml:lang="en">The toxicity and mutagenicity of three DNA adducts formed by the anticancer drug cis-diamminedichloroplatinum(II) (cis-DDP or cisplatin) were investigated in Escherichia coli. The adducts studied were cis-[Pt(NH3)2(d(GpG))] (G*G*), cis-[Pt(NH3)2(d(ApG))] (A*G*) and cis-[Pt(NH3)2(d(GpTpG))] (G*TG*), which collectively represent approximately 95% of the DNA adducts reported to form when the drug damages DNA. Oligonucleotide 24-mers containing each adduct were positioned at a known site within the viral strand of single stranded M13mp7L2 bacteriophage DNA. Following transfection into E. coli DL7 cells, the genomes containing the G*G*, A*G* and G*TG* adducts had survival levels of 5.2 +/- 1.2, 22 +/- 2.6 and 14 +/- 2.5% respectively, compared to unmodified genomes. Upon SOS induction, the survival of genomes containing the G*G* and A*G* adducts increased to 31 +/- 5.4 and 32 +/- 4.9% respectively. Survival of the genome containing the G*TG* adduct did not increase upon SOS induction. In SOS induced cells, the G*G* and A*G* adducts gave rise predominantly to G-->T and A-->T transversions respectively, targeted to the 5' modified base. In addition, A-->G transitions were detected for the A*G* adduct and low levels of tandem mutations at the 5' modified base as well as the adjacent 5' base were also observed for both adducts. The A*G* adduct was more mutagenic than the G*G* adduct, with a mutation frequency of 6% compared to 1.4% for the latter adduct. No cis-[Pt(NH3)2)2+ intrastrand crosslink-specific mutations were observed for the G*TG* adduct.</div>
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Mutagenic and genotoxic effects of DNA adducts formed by the anticancer drug cis-diamminedichloroplatinum(II).

Mutagenic and genotoxic effects of DNA adducts formed by the anticancer drug cis-diamminedichloroplatinum(II).

Source :

Descripteurs français

English descriptors

Abstract

Links toward previous steps (curation, corpus...)

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