title: Iron overload as a major targetable pathogenesis of asbestos-induced mesothelial carcinogenesis.
abstract: Few people expected that asbestos, a fibrous mineral, would be carcinogenic to humans. In fact, asbestos is a definite carcinogen in humans, causing a rare but aggressive cancer called malignant mesothelioma (MM). Mesothelial cells line the three somatic cavities and thus do not face the outer surface, but reduce the friction among numerous moving organs. MM has several characteristics: extremely long incubation period of 30-40 years after asbestos exposure, difficulty in clinical diagnosis at an early stage, and poor prognosis even under the current multimodal therapies. In Japan, 'Kubota shock' attracted considerable social attention in 2005 for asbestos-induced mesothelioma and, thereafter, the government enacted a law to provide the people suffering from MM a financial allowance. Several lines of recent evidence suggest that the major pathology associated with asbestos-induced MM is local iron overload, associated with asbestos exposure. Preclinical studies to prevent MM after asbestos exposure with iron reduction are in progress. In addition, novel target genes in mesothelial carcinogenesis have been discovered with recently recognized mesothelioma-prone families. Development of an effective preventive strategy is eagerly anticipated because of the long incubation period for MM.
authors.forename: Shinya
authors.initials: S
authors.lastname: Toyokuni
mesh_terms: D000327:Adsorption; D000818:Animals; D001194:Asbestos / Q000009:adverse effects*; D001195:Asbestosis / Q000150:complications / Q000453:epidemiology; D001565:Benzoates / Q000627:therapeutic use; D002274:Carcinogens, Environmental / Q000493:pharmacokinetics; D002292:Carcinoma, Renal Cell / Q000139:chemically induced / Q000235:genetics; D002471:Cell Transformation, Neoplastic; D055028:Comparative Genomic Hybridization; D000077588:Deferasirox; D005290:Ferric Compounds / Q000633:toxicity; D000077605:Ferric Oxide, Saccharated; D019942:Genes, p16; D005937:Glucaric Acid / Q000633:toxicity; D006801:Humans; D007502:Iron Chelating Agents / Q000627:therapeutic use; D019190:Iron Overload / Q000188:drug therapy / Q000209:etiology* / Q000628:therapy; D007564:Japan / Q000453:epidemiology; D007680:Kidney Neoplasms / Q000139:chemically induced / Q000235:genetics; D008297:Male; D008654:Mesothelioma / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics / Q000517:prevention & control; D019016:Mineral Fibers / Q000009:adverse effects; D010534:Peritoneal Neoplasms / Q000139:chemically induced; D018962:Phlebotomy; D010997:Pleural Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics / Q000517:prevention & control; D051381:Rats; D014230:Triazoles / Q000627:therapeutic use
chemical_list: D001565:Benzoates; D002274:Carcinogens, Environmental; D005290:Ferric Compounds; D007502:Iron Chelating Agents; D019016:Mineral Fibers; D014230:Triazoles; D001194:Asbestos; D000077605:Ferric Oxide, Saccharated; D005937:Glucaric Acid; D000077588:Deferasirox
keywords: Asbestos; CDKN2A/2B; Iron chelation; Iron overload; Malignant mesothelioma; Phlebotomy