ArticleCancer chemotherapy and pharmacology2009
The Werner's syndrome 4330T>C (Cys1367Arg) gene variant does not affect the in vitro cytotoxicity of topoisomerase inhibitors and platinum compounds.
Article in Cancer chemotherapy and pharmacology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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3 citing papers in PubMed, 4 citations in OpenAlex.
- Population-based in vitro hazard and concentration-response assessment of chemicals: the 1000 genomes high-throughput screening study.Environmental health perspectives · 2015Article
- Predictive impact of genetic polymorphisms in DNA repair genes on susceptibility and therapeutic outcomes to colorectal cancer patients.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015Article
- Pharmacogenomic discovery using cell-based models.Pharmacological reviews · 2009Review
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12 authors at 4 institutions in 1 country.
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Abstract
purposeWerner's syndrome (WS) is a recessive disorder of premature onset of processes associated with aging. Defective DNA repair has been reported after exposure of cells isolated from WS patients to DNA-damaging agents. The germline 4330T>C (Cys1367Arg) variant in the WS gene (WRN) has been associated with protection from age-related diseases, suggesting it has a functional role. We studied whether the 4330T>C variant confers altered drug sensitivity in vitro.
methods4330T>C was genotyped in 372 human lymphoblastoid cell lines (LCLs) from unrelated healthy Caucasian individuals using a TaqMan-based method. The study was powered to detect the effect of the 4330T>C genotypes after exposure to camptothecin (based upon preliminary data). The effect of the 4330T>C variant on the cytotoxicity of etoposide, carboplatin, cisplatin and daunorubicin was also tested. WRN expression in 57 LCLs was measured by microarray.
resultsNo significant difference between the IC50 of the cells was observed among genotypes (P = 0.46) after exposure to camptothecin. No association was also observed for etoposide, carboplatin, cisplatin, and daunorubicin (ANOVA, P > 0.05). WRN expression also did not vary across genotypes (ANOVA, P = 0.37).
conclusionThese results suggest that this nonsynonymous variant has relatively normal function at the cellular level.
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