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• W72818518 abstract "An association between chronic inflammation and cancer is supported by both clinical observations and laboratory studies. Using laboratory models, there is evidence that suggests tumour promoters such as 12-0-tetradecanoylphorbol-13-acetate (TPA) can activate inflammatory cells to release DNAdamaging agents. These agents include reactive oxygen species (ROS) such as superoxide anion and hydrogen peroxide as well as products of lipid peroxidation and arachidonic acid metabolism. A current hypothesis is that these agents damage DNA in nearby cells. DNA damage that is not repaired in a tissue can elevate chromosomal instability and increase the probability of acquiring the genetic alterations that are required for carcinogenesis. The hypothesis tested in this thesis was that the genotype of a nearby cell may influence its sensitivity to the DNA-damaging agents. Altered sensitivity may be inborn or may be acquired during the process of carcinogenesis. For example, a number of tumour cell lines and cells from the cancer-prone syndrome Ataxia-telangiectasia (AT) show increased sensitivity to radiation-induced DNA damage, an effect that has been attributed to a DNA repair defect located on chromosome 11. A role of loci on chromosome 11 in determining a cell's sensitivity to I genetic damage was assayed during co-culture of epithelial and fibroblast cells I with TPA-activated neutrophils or with exposure to xanthinelxanthine oxidase I I (WXO). The micronucleus (MN) assay was used to quantify chromosomal I I breakage and the comet assay the amount of initial strand breakage and the rate ~ I of rejoining of these breaks during DNA repair. Two model systems were studied: a bladder carcinoma model and an AT model. ' In the first model, the results showed that bladder carcinoma cells I I exposed to TPA-activated neutrophils and WXO were partially protected from 1 MN induction by the microcell-mediated insertion of normal chromosome 11 ~" @default.
• W72818518 created "2016-06-24" @default.
• W72818518 creator A5063281632 @default.
• W72818518 date "1994-01-01" @default.
• W72818518 modified "2023-09-27" @default.
• W72818518 title "The role of chromosome 11 in determining cell sensitivity to DNA-damaging agents released by activated inflammatory cells" @default.
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• W72818518 hasPublicationYear "1994" @default.
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