Robert W Rees

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The battery of genetic toxicity tests required by most regulatory authorities includes both bacterial and mammalian cell assays and identifies practically all genotoxic carcinogens. However, the relatively high specificity of the Salmonella mutagenicity assay (Ames test) is offset by the low specificity of the established mammalian cell assays, which leads(More)
Although the application of the concept of a threshold to risk assessment is widespread, there remains little experimental evidence for the existence of thresholds for genotoxic compounds, other than aneugens. The clastogenicity of topoisomerase inhibitors is believed to result from the transient stabilization of the topoisomerase enzyme with DNA during the(More)
The GADD45a-GFP (GreenScreen HC) reporter assay detects genotoxic damage in the human lymphoblastoid TK6 cell line and gives positive results for all classes of genotoxin, including mutagens, aneugens and clastogens. In this study, a collection of 75 marketed pharmaceuticals were tested in the assay. Compounds in the collection represent a broad range of(More)
A new protocol has recently been developed and validated for the GreenScreen HC GADD45a-GFP genotoxicity reporter assay, enabling the incorporation of an S9 metabolic activation system into the assay. The S9 protocol employs flow-cytometric methodology for the detection of both reporter GFP fluorescence and propidium iodide fluorescence for the estimation(More)
Sixteen coded compounds were blind-tested at 4 laboratories using the recently described GADD45a-GFP genotoxicity assay. The compounds were chosen to include non-genotoxic compounds as well as weak and strong genotoxins. None of the compounds required metabolic activation in order to exhibit genotoxic effects. The participating laboratories included 2(More)
In the accompanying paper (Kleinman et al., submitted for publication), the link between phototoxicity and photoreactivity (i.e. production of singlet oxygen, superoxide and chemical photostability) has been established. It is proposed this may be used to refine existing triggers for photosafety testing. Using a series of compounds we have determined(More)
The utility of rank transformation followed by parametric analysis of the ranks has been assessed for determination of the statistical significance of genotoxicity data. Both nonparametric and parametric analytical methods have defects when used to assess the significance of results from routine regulatory tests. Superficially, the rank transformation(More)
There is considerable concern regarding the biological plausibility of the response of certain chemicals in the in vitro photoclastogenicity assay, suggesting that this assay is oversensitive and lacks specificity. To explore this further, four coded compounds (aminotriazole, propantheline bromide, cycloheximide and disulfoton) were evaluated for their(More)
Bladder cancer evolves via the accumulation of numerous genetic alterations, with loss of p53 and p16 function representing key events in the development of malignant disease. In addition, components of the epidermal growth factor receptor (EGFR) signaling pathway are frequently overexpressed, providing potential chemotherapeutic targets. We have previously(More)
The pH 6.7 Syrian hamster embryo (SHE) cell morphological transformation assay is a short-term in vitro test that has been used to predict rodent carcinogenicity. Previous reports have indicated that the SHE assay has an overall concordance of approximately 80% with the 2 year rodent bioassay. We selected five compounds, genistein, metaproterenol, rotenone,(More)