title: Carcinogen metabolism studies in human bronchial and lung parenchymal tissues.
abstract: The pulmonary metabolism of xenobiotics was investigated by measuring the glutathione content and the activity of the aryl hydrocarbon hydroxylase, epoxide hydrolase, glutathione S-transferase, and uridine 5' -diphosphoglucuronosyl transferase enzymes in S-12 fractions of bronchial tree and peripheral lung parenchyma obtained at surgery from 21 patients. In parallel, the same preparations were used to assess either the activation of promutagens, i.e., benzo(a)pyrene, 2-aminofluorene, cyclophosphamide, and a cigarette smoke condensate, to metabolites reverting his- Salmonella typhymurium strains, or the decrease of direct-acting mutagens, i.e., sodium dichromate, 4-nitroquinoline N-oxide, epichlorohydrin, and ICR 191. As compared to bronchus preparations, parenchymal preparations contained considerably higher concentrations of reduced glutathione, had a significantly higher epoxide hydrolase activity, and, as assessed by means of a quantitative index, were more efficient in activating 2-aminofluorene and in reducing the mutagenicity of dichromate and 4-nitroquinoline N-oxide. These data may suggest that parenchymal lung tissue is more capable than bronchial tissue to detoxify reactive intermediates of xenobiotics, possibly explaining the greater susceptibility of bronchi to cigarette smoke-induced cancers.
authors.affiliation: CNR Institute of Clinical Physiology, University of Pisa, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Petruzzelli
authors.forename: S
authors.initials: S
authors.lastname: De Flora
authors.forename: M
authors.initials: M
authors.lastname: Bagnasco
authors.forename: E
authors.initials: E
authors.lastname: Hietanen
authors.forename: A M
authors.initials: AM
authors.lastname: Camus
authors.forename: R
authors.initials: R
authors.lastname: Saracci
authors.forename: A
authors.initials: A
authors.lastname: Izzotti
authors.forename: H
authors.initials: H
authors.lastname: Bartsch
authors.forename: C
authors.initials: C
authors.lastname: Giuntini
mesh_terms: D015112:4-Nitroquinoline-1-oxide / Q000378:metabolism; D000585:Aminacrine / Q000031:analogs & derivatives / Q000378:metabolism; D001564:Benzo(a)pyrene / Q000378:metabolism; D001980:Bronchi / Q000378:metabolism*; D002840:Chromates / Q000378:metabolism; D003520:Cyclophosphamide / Q000378:metabolism; D004811:Epichlorohydrin / Q000378:metabolism; D005449:Fluorenes / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008168:Lung / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009153:Mutagens / Q000378:metabolism*; D009588:Nitrogen Mustard Compounds / Q000378:metabolism; D013638:Tars / Q000378:metabolism
chemical_list: D002840:Chromates; D005449:Fluorenes; D009153:Mutagens; D009588:Nitrogen Mustard Compounds; D013638:Tars; C024746:tobacco tar; D004811:Epichlorohydrin; D001564:Benzo(a)pyrene; C012177:2-aminofluorene; D015112:4-Nitroquinoline-1-oxide; D000585:Aminacrine; D003520:Cyclophosphamide; C004294:acridine half-mustard; C016104:sodium bichromate