ArticleMutagenesis2021
A comparative analysis of the mutagenicity of platinum-containing chemotherapeutic agents reveals direct and indirect mutagenic mechanisms.
Article in Mutagenesis, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 35 citations in OpenAlex.
- Article
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- Artichoke Extract Ameliorates CCl4-Induced Hepatocellular Carcinoma in Albino Rats by Regulating the Phosphatidylinositol 3-kinase/serine-threonine Protein Kinase Pathway.Anti-cancer agents in medicinal chemistry · 2026Article
- Collateral mutagenesis funnels multiple sources of DNA damage into a ubiquitous mutational signature.bioRxiv : the preprint server for biology · 2025Article
- DiffInvex identifies evolutionary shifts in driver gene repertoires during tumorigenesis and chemotherapy.Nature communications · 2025Article
- Prenatal Exposure to Chemotherapy Increases the Mutation Burden in Human Neonatal Hematopoietic Stem Cells.Cancer discovery · 2025Article
- Tracking the Evolution of Cutaneous Melanoma by Multiparameter Flow Sorting and Genomic Profiling.International journal of molecular sciences · 2025Article
- Comprehensive whole-genome sequencing reveals origins of mutational signatures associated with aging, mismatch repair deficiency and temozolomide chemotherapy.Nucleic acids research · 2025Article
- Nanocarrier-mediated cancer therapy with cisplatin:Heliyon · 2024Article
- Mutational profile of the regenerative process and de novo genome assembly of the planarian Schmidtea polychroa.Nucleic acids research · 2024Article
- DNA mismatch repair protects the genome from oxygen-induced replicative mutagenesis.Nucleic acids research · 2023Article
- Article
- Experimental systems for the analysis of mutational signatures: no 'one-size-fits-all' solution.Biochemical Society transactions · 2023Article
- Integrative Pan-Cancer Genomic and Transcriptomic Analyses of Refractory Metastatic Cancer.Cancer discovery · 2023Article
- Homologous recombination deficiency signatures in gastrointestinal and thoracic cancers correlate with platinum therapy duration.NPJ precision oncology · 2023Article
- Characterisation of the spectrum and genetic dependence of collateral mutations induced by translesion DNA synthesis.PLoS genetics · 2022Article
- BRCA1 deficiency specific base substitution mutagenesis is dependent on translesion synthesis and regulated by 53BP1.Nature communications · 2022Article
- Activation of DNA Damage Tolerance Pathways May Improve Immunotherapy of Mesothelioma.Cancers · 2021Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Platinum-based drugs are a mainstay of cancer chemotherapy. However, their mutagenic effect can increase tumour heterogeneity, contribute to the evolution of treatment resistance and also induce secondary malignancies. We coupled whole genome sequencing with phenotypic investigations on two cell line models to compare the magnitude and examine the mechanism of mutagenicity of cisplatin, carboplatin and oxaliplatin. Cisplatin induced significantly more base substitution mutations than carboplatin or oxaliplatin when used at equitoxic concentrations on human TK6 or chicken DT40 cells, and also induced the highest number of short insertions and deletions. The analysis of base substitution spectra revealed that all three tested platinum drugs elicit both a direct mutagenic effect at purine dinucleotides, and an indirect effect of accelerating endogenous mutagenic processes, whereas the direct mutagenic effect appeared to correlate with the level of DNA damage caused as assessed through histone H2AX phosphorylation and single-cell agarose gel electrophoresis, the indirect mutagenic effects were equal. The different mutagenicity and DNA-damaging effect of equitoxic platinum drug treatments suggest that DNA damage independent mechanisms significantly contribute to their cytotoxicity. Thus, the comparatively high mutagenicity of cisplatin should be taken into account in the design of chemotherapeutic regimens.
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