Iron is the most abundant transition metal in biological systems and is required to facilitate key metabolic reactions, including DNA synthesis, oxygen transport and cellular respiration. The distribution of iron within the body is carefully regulated to prevent the generation of cytotoxic reactive oxygen species. The investigations described in this book were aimed to understand the mechanisms and diseases associated with mammalian iron metabolism. Specifically, Chapter 3 investigates the systemic iron homeostatic activity of hepcidin, the hormone of iron metabolism, while bound to the blood carrier protein, 2-macroglobulin; Chapter 4 examines the molecular mechanism(s) involved in the perturbation of cellular iron metabolism that results in mitochondrial iron-accumulation in Friedreich's ataxia; and Chapter 5 explores the molecular links between mitochondrial iron-dysregulation and the fatal cardiac defects in Friedreich's ataxia.

Previous studies demonstrated that thiosemicarbazone iron chelator possessed potent and selective anti-cancer activity. In this study, the in vitro and in vivo anti-tumor efficacy and tolerability of 2-benzoylpyridine thiosemicarbazone (BpT) iron chelators were examined. The BpT chelators were tested against human lung cancer cells in vitro and tumor xenografts in mice. The toxicity of Bp44mT and its effects on the expression of iron-regulated molecules involved in growth and cell cycle control were investigated. The results shown demonstrate the anti-tumor activity of the orally-active Bp44mT chelator, which was well tolerated in vivo. Furthermore, the cytotoxicity of thiosemicarbazones is likely to be mediated, in part, through their redox activity and effects on multiple thiol-containing systems. In terms of signal transduction, iron chelation may influence the MAPK signaling pathways via the thioredoxin-ASK1 signalosome. These results emphasize the importance of redox-activity of thiosemicarbazone chelators. Considering their potent anti-tumor activity, these investigations facilitate the future development of promising thiosemicarbazone iron chelators as anti-cancer agents.

Previous studies demonstrated that HDpT chelators have potent anti-tumour activity. We have now designed and generated two new groups of chelators, HBpT and HNBpT. Comparing the three series of chelators, the HBpT analogues displayed highest anti- proliferative efficacy against SK-N-MC neuroepithelioma cells and was greater than other well known chelators (DFO, Triapine and 311). Three analogues of the HBpT series displayed much greater anti-proliferative activity against SK-N-MC cells than normal MRC-5 fibroblasts, indicating their selectivity against tumour cells. Structure-activity relationships examination demonstrated that lipophilicity and redox cycling activity were important factors in generating potent chelators. Redox activity determined by ascorbate oxidation and benzoate hydroxylation assays showed that the HBpT ligands were the most active chelators. Microarray studies using DFO and HDp44mT, demonstrated up- regulation of the gene in cell cycle arrest, while genes in cancer progression were down-regulated. The current studies have identified a novel group of chelators with the greatest activity of all chelators previously prepared in our lab.

The potato is one of the world's most important food crops. It produces more nutritious food from less land in a shorter time than any other major crop. Therefore advances in the production of new potato varieties will greatly contribute to the world's food supply. The book outlines strategies used in the breeding and testing of potato varieties. It considers prospects for varietal improvement using both traditional and new techniques, including genetic manipulation, tissue culture and protoplast fusion. Opportunities for breeding varieties suitable for propagation from true seed, of particular significance to the agricultural systems of developing countries, are also featured, together with an extensive and bibliography. The book is based on the proceedings of a joint meeting of EAPR and EUCARPIA at King's College, Cambridge, December 1985. It contains contributions from many leading authorities in potato breeding and variety assessment throughout the world, and will interest post-graduate students in plant breeding, genetics and molecular biology, together with professionals engaged in potato research and the application of molecular biology to agriculture.

The potato is one of the world's most important food crops. It produces more nutritious food from less land in a shorter time than any other major crop. Therefore advances in the production of new potato varieties will greatly contribute to the world's food supply. The book outlines strategies used in the breeding and testing of potato varieties. It considers prospects for varietal improvement using both traditional and new techniques, including genetic manipulation, tissue culture and protoplast fusion. Opportunities for breeding varieties suitable for propagation from true seed, of particular significance to the agricultural systems of developing countries, are also featured, together with an extensive and bibliography. The book is based on the proceedings of a joint meeting of EAPR and EUCARPIA at King's College, Cambridge, December 1985. It contains contributions from many leading authorities in potato breeding and variety assessment throughout the world, and will interest post-graduate students in plant breeding, genetics and molecular biology, together with professionals engaged in potato research and the application of molecular biology to agriculture.