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      Medical Applications and Toxicities of Gallium Compounds

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          Abstract

          Over the past two to three decades, gallium compounds have gained importance in the fields of medicine and electronics. In clinical medicine, radioactive gallium and stable gallium nitrate are used as diagnostic and therapeutic agents in cancer and disorders of calcium and bone metabolism. In addition, gallium compounds have displayed anti-inflammatory and immunosuppressive activity in animal models of human disease while more recent studies have shown that gallium compounds may function as antimicrobial agents against certain pathogens. In a totally different realm, the chemical properties of gallium arsenide have led to its use in the semiconductor industry. Gallium compounds, whether used medically or in the electronics field, have toxicities. Patients receiving gallium nitrate for the treatment of various diseases may benefit from such therapy, but knowledge of the therapeutic index of this drug is necessary to avoid clinical toxicities. Animals exposed to gallium arsenide display toxicities in certain organ systems suggesting that environmental risks may exist for individuals exposed to this compound in the workplace. Although the arsenic moiety of gallium arsenide appears to be mainly responsible for its pulmonary toxicity, gallium may contribute to some of the detrimental effects in other organs. The use of older and newer gallium compounds in clinical medicine may be advanced by a better understanding of their mechanisms of action, drug resistance, pharmacology, and side-effects. This review will discuss the medical applications of gallium and its mechanisms of action, the newer gallium compounds and future directions for development, and the toxicities of gallium compounds in current use.

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          The cell biology of bone metabolism.

          Satya S. Varanasi, Raymond H W Ng, Godfrey J A Walker … (2008)
          Contrary to the commonly held misconception, bone is a relatively dynamic organ that undergoes significant turnover as compared to other organs in the body. This review details how complex intercellular signalling, between the osteoprogenitor cells and mature osteoblasts, osteocytes and osteoclasts, regulates and balances activities of bone cells during remodelling and growth. Both systemic, as well as local autocrine and paracrine factors are discussed. A number of recent important advances in cell biology of bone have led to a new paradigm in understanding of the subject. In this regard, the interaction between the immune system and bone cells is of particular interest, leading to the emergence of a new discipline termed osteoimmunology. The role of lymphocytes and a number of key cytokines in the regulation of osteoclastogenesis and osteoblast function is critically examined. The intracellular signalling regulating key cellular pathways involved in cell differentiation and activity are outlined. The emerging evidence of osteocytes as mechanosensors as well as regulators of mineralisation is discussed.
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            Antitumour metal compounds: more than theme and variations.

            Christian Hartinger, Michael A. Jakupec, Vladimir Arion … (2008)
            Triggered by the resounding success of cisplatin, the past decades have seen tremendous efforts to produce clinically beneficial analogues. The recent achievement of oxaliplatin for the treatment of colon cancer should, however, not belie the imbalance between a plethora of investigated complexes and a very small number of clinically approved platinum drugs. Strategies opening up new avenues are increasingly being sought using complexes of metals other than platinum such as ruthenium or gallium. Based on the chemical differences between these metals, the spectrum of molecular mechanisms of action and potential indications can be broadened substantially. Other approaches focus on complexes with tumour-targeting properties, thereby maximizing the impact on cancer cells and minimizing the problem of adverse side effects, and complexes with biologically active ligands.
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              Ribonucleotide reductases.

              P Reichard, Margaret Jordan (1997)
              Ribonucleotide reductases provide the building blocks for DNA replication in all living cells. Three different classes of enzymes use protein free radicals to activate the substrate. Aerobic class I enzymes generate a tyrosyl radical with an iron-oxygen center and dioxygen, class II enzymes employ adenosylcobalamin, and the anaerobic class III enzymes generate a glycyl radical from S-adenosylmethionine and an iron-sulfur cluster. The X-ray structure of the class I Escherichia coli enzyme, including forms that bind substrate and allosteric effectors, confirms previous models of catalytic and allosteric mechanisms. This structure suggests considerable mobility of the protein during catalysis and, together with experiments involving site-directed mutants, suggests a mechanism for radical transfer from one subunit to the other. Despite large differences between the classes, common catalytic and allosteric mechanisms, as well as retention of critical residues in the protein sequence, suggest a similar tertiary structure and a common origin during evolution. One puzzling aspect is that some organisms contain the genes for several different reductases.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Int J Environ Res Public Health
                Journal ID (publisher-id): 101238455
                Title: International Journal of Environmental Research and Public Health
                Publisher: Molecular Diversity Preservation International (MDPI)
                ISSN (Print): 1661-7827
                ISSN (Electronic): 1660-4601
                Publication date (Electronic): 10 May 2010
                Publication date (Print): May 2010
                Volume: 7
                Issue: 5
                Pages: 2337-2361
                Affiliations
                Division of Neoplastic Diseases, Department of Medicine, Medical College of Wisconsin, 9200 West Wisconsin Avenue, Milwaukee, WI 53226, USA; E-Mail: chitambr@ 123456mcw.edu ; Tel.: +1-414-805-4600; Fax: +1-414-805-4606
                Article
                Publisher ID: ijerph-07-02337
                DOI: 10.3390/ijerph7052337
                PMC ID: 2898053
                PubMed ID: 20623028
                SO-VID: 7eed48fb-ea10-416c-b0d7-37ca89d9a549
                Copyright © © 2010 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland.
                License:

                This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                Date received : 28 January 2010
                Date revision received : 24 March 2010
                Date accepted : 31 March 2010
                Categories
                Subject: Review

                ScienceOpen disciplines: Public health
                Keywords: toxicities,calcium and bone metabolism,cancer therapeutics,iron proteins,iron,semi-conductors,gallium,electronics
                Data availability:
                ScienceOpen disciplines: Public health
                Keywords: toxicities, calcium and bone metabolism, cancer therapeutics, iron proteins, iron, semi-conductors, gallium, electronics

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