title: Genomic structure and genetic mapping of the human neutral cysteine protease bleomycin hydrolase.
abstract: Bleomycin hydrolase (BH) is the only known eukaryotic enzyme that inactivates the widely used antineoplastic agent bleomycin (BLM) and is a primary candidate gene for protection against lethal BLM-induced pulmonary fibrosis and for BLM resistance in tumors. Human BH was found to exist as a single gene that was mapped to chromosome 17 using National Institute of General Medical Sciences human/rodent hybrid mapping panels and localized to 17q11.1-11.2 by linkage analysis using the Centre d'Etude du Polymorphisme Humain reference database. The human BH gene consisted of 11 exons ranging in size from 69-198 bp separated by introns of approximately 1 kb, reflecting the archetypal genomic structure of the cysteine protease family. A polymorphic site was identified in the eleventh exon at bp 1450 encoding either valine or isoleucine. These findings provide essential tools required to define the role of BH in BLM-induced pulmonary fibrosis and BLM resistance in tumors.
authors.affiliation: Department of Human Genetics, University of Pittsburgh, Pennsylvania 15261, USA.
authors.forename: S E
authors.initials: SE
authors.lastname: Montoya
authors.forename: R E
authors.initials: RE
authors.lastname: Ferrell
authors.forename: J S
authors.initials: JS
authors.lastname: Lazo
mesh_terms: D000818:Animals; D001483:Base Sequence; D001761:Bleomycin / Q000009:adverse effects; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D003546:Cysteine Endopeptidases / Q000235:genetics*; D004198:Disease Susceptibility; D019008:Drug Resistance, Neoplasm; D005091:Exons / Q000235:genetics; D005796:Genes; D006801:Humans; D006822:Hybrid Cells; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000235:genetics
chemical_list: D001761:Bleomycin; D003546:Cysteine Endopeptidases; C031262:bleomycin hydrolase