Threshold Effect of Free Radical Quenching in a Progressive Breast Cancer Cell Line Model

Oxidative stress is a consequence of both normal and abnormal cellular metabolism and is linked to cell proliferation, differentiation and apoptosis leading to the development of human diseases. A common mechanism for chemotherapeutic agents inducing cell death is through the generation of free radicals. Although the exact mechanism of the molecular signalling that it entails is still being worked upon, it is clear that this varies with the stage and type of cancer and the drug and dosage used. We study the response of MCF10A series progressive breast cancer cell lines, in response to Adriamycin and Cyclophosphamide. A targeted set of candidate genes from these pathways that participate in free radical metabolism were evaluated for gene expression. Genes in oxidative stress response pathways were modelled earlier using the multivariate Boolean Network Modelling. We provide evidence that the strategy of using Boolean modelling and laboratory testing of the model, although not a perfect match, has potential to contribute in biology. We present a novel and testable “threshold” model of free radical generation that is dependent on the quantity of free radical generation. Using logic tools like Boolean circuitry, with fine-tuned experiments may serve a useful purpose in designing preclinical chemotherapic protocols.his document gives formatting instructions for authors preparing papers for publication in this journal. All authors must follow the instructions given in this document for the papers to be published.