Cytotoxic Mechanisms of Iron Chelators with Therapeutic Potential

ISBN-13: 9783639147803 / Angielski / Miękka / 2009 / 172 str.

Timothy Chaston

Opis

For many years iron chelators have been used for thetreatment of iron overload disease and cancer.Nonetheless, the development of novel syntheticchelators with improved bioavaliability and reducedcytotoxicity remains an area of much interest. Thisthesis is an examination of some mechanisms throughwhich iron binding agents cause toxicity. Two novelclasses of iron chelator were compared to clinicallyrelevant chelators with a range of cytotoxicprofiles. A variety of assays were employed tocategorise these agents in terms of their capacity towithdraw iron from cells, to generate oxygen radicalsand to damage to DNA. In correlating these propertieswith in vitro effects on proliferation it emergesthat toxicity of iron chelators arises from cellulariron deprivation, the induction of oxidative stressand biomolecular localisation of oxygen radicals. In identifying functional structural elements andiron binding motifs this work indicates biologicalconsequences to be considered in the design of ironbinding chemotherapeutic agents.

O autorze

Timothy Chaston:
Timothy B. Chaston, B.AppSci, Ph.D.: Post Doctoral Research
Associate, Kings College London, London, UK.
Des Richardson:
Des R. Richardson, B.Sc., M.Sc., Ph.D., D.Sc: Professor of
Cancer Cell Biology, NHMRC Senior Principal Research Fellow,
Director of Iron Metabolism and Chelation Program, University of
Sydney, Sydney, Australia.