title: Biochemical pathology of lung damage produced by chemicals.
abstract: Damage to the lung may be caused by chemicals that gain access to the alveolar zone by inhalation or via the pulmonary circulation. Several agents toxic to the lung have recently been found to bind covalently to pulmonary macromolecules or to disrupt certain metabolic reactions. However, it has also been observed that extensive chemical lung injury is not necessarily preceded by a depression of pulmonary metabolic reactions. One possible explanation for this might be that biochemical changes due to cell death are often masked and/or compensated for by changes associated with lung tissue repair. Substantial cell proliferation as a response to toxic lung damage is a common phenomenon in lung pathology. This makes it necessary to develop models that permit analysis of the biochemical events triggering and accompanying cell growth in lung. We have recently examined some aspects of cell proliferation in mouse lung. Intraperitoneal injection of the antioxidant butylated hydroxytoluene (BHT) produces within 3-5 days extensive hypertrophy, hyperplasia, and general disorganization of the cellular components of the lung. Total lung weight and total DNA per lung almost double within this time and are accompanied by proportional increases in protein and lipids. RNA accumulates at a faster rate than DNA. The changes in lung composition are accompanied by dose-dependent increases in the in vivo incorporation of thymidine into DNA and of leucine into protein. The activities of several enzymes (thymidine kinase, DNA polymerase, uridine kinase, glucose-6-phosphate dehydrogenase, and 5'-nucleotidase) increase substantially after BHT. Administration of BHT to mice seems to offer a convenient tool to study cell growth in the lungs of mice.
mesh_terms: D000818:Animals; D002084:Butylated Hydroxytoluene / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003408:Cresols / Q000494:pharmacology*; D004254:DNA Nucleotidyltransferases / Q000378:metabolism; D004261:DNA Replication / Q000187:drug effects; D004048:Diethylamines / Q000494:pharmacology; D006965:Hyperplasia / Q000139:chemically induced; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D051379:Mice; D008854:Microscopy, Electron; D008954:Models, Biological; D009602:Nitrosamines / Q000494:pharmacology; D010269:Paraquat / Q000494:pharmacology; D012313:RNA / Q000096:biosynthesis; D013937:Thymidine Kinase / Q000378:metabolism; D014541:Uridine Kinase / Q000378:metabolism
chemical_list: D003408:Cresols; D004048:Diethylamines; D009602:Nitrosamines; D002084:Butylated Hydroxytoluene; D012313:RNA; D013937:Thymidine Kinase; D014541:Uridine Kinase; D004254:DNA Nucleotidyltransferases; D010269:Paraquat