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Biomedical subjects

H Witschi

Publications and source records attributed to H Witschi.

At least 109 records · Page 6Linked to original sources
PubMed1977

Inhibition of butylated hydroxytoluene-induced mouse lung cell division by oxygen: time-effect and dose-effect relationships.

Mice were injected i.p. with 250 or 400 mg/kg of butylated hydroxytoluene (BHT). In vivo incorporation of thymidine into pulmonary DNA was measured on days 1-7 after BHT. 2, 3 and 4 days after BHT, DNA synthesis was inhibited by a 24-h exposure to 100% oxygen, whereas on days 5, 6 and 7 after BHT, oxygen failed to depress synthesis. A similar pattern was observed when incorporation of leucine into protein was measured: 2 and 4 days after BHT, oxygen decreased leucine incorporation, but had no effect 6 days after BHT or in animals not pretreated with BHT. It is concluded that the cells proliferating early after BHT, the type II alveolar cells, are more susceptible to the cytotoxic effects of oxygen than are interstitial and capillary endothelial cells.

Animals↗
PubMed1977

Enhancement of urethan tumorigenesis in mouse lung by butylated hydroxytoluene.

Intraperitoneal injection of the antioxidant butylated hydroxytoluene (BHT) produces cell proliferation in mouse lungs within 2-4 days. We examined whether the presence of an increased number of proliferating lung cells would influence urethan tumorigenesis. Male Swiss-Webster mice were treated with 1 mg urethan/g before, during, or after BHT-stimulated cell growth in the lung. The number of pulmonary tumors found 13-15 weeks later was not different in BHT-treated mice compared to that in controls. On the other hand, repeated stimulation of cell growth after urethan treatment enhanced tumorigenesis. Male Swiss-Webster and A/J mice were given a single dose of urethan (1 mg/g) and, beginning 7 days later, weekly injections of BHT or corn oil. Repeated injections of BHT significantly increased the yield of lung tumors in both strains. Weekly injections of BHT into mice pretreated with 0.9% NaCl reduced the number of spontaneous pulmonary adenomas.

Animals↗
PubMed1977

Environmental agents altering lung biochemistry.

Environmental agents may enter the lung via the tracheobronchial tree or via the bloodstream. They can interact with lung cell metabolism and set in motion a sequence of events that leads to damage, adaptation, and repair. Biochemical signs of lung damage described include lipid peroxidation, decreased biosynthesis of macromolecules, depressed enzyme activities, and the binding of metabolites of the offending agent to tissue macromolecules. As a response to acute damage, lung can activate several biochemical pathways. The selenium-glutathione peroxidase system affords protection against lipid peroxidation and increased activity of superoxide dismutase provides oxygen tolerance. Biochemical adaptation occasionally occurs very quickly: the herbicides paraquat and diquat produce an acute loss of cellular NADPH in lung. This is accompanied by a sudden increase in pentose phosphate pathway activity. Biochemical events accompanying tissue repair following lung injury are increased synthesis of nucleic acids and of protein and enhanced enzymatic activity. The repair following lung damage caused by drugs may be inhibited by oxygen.

Animals↗
PubMed1977

Lung injury induced by butylated hydroxytoluene: cytodynamic and biochemical studies in mice.

Butylated hydroxytoluene, a common food additive, is known to produce proliferative pulmonary changes characterized by increased DNA, RNA, and lung weight. In the present study, reactive hyperplasia and fibrosis were produced within 9 days after a single intraperitoneal injection of 400 mg. per kg. of butylated hydroxytoluene was given to mice. Initial perivascular edema with cell infiltrates was followed by necrosis of type 1 alveolar epithelial cells and by division of type 2 cells which repopulated the alveolar wall with unusually large epithelial cells containing abundant cytoplasm. DNA synthesis, as indexed by thymidine and uridine kinase levels and by 3H-thymidine uptake, increased at 2 days, peaked at 4 days, and dropped gradually to near normal by day 9. Differential counts of labeled cells revealed that the early rise was due to epithelial cell proliferation; in turn, interstitial and endothelial cells entered the proliferative phase. Endothelial labeling peaked at day 6 immediately following ultrastructural evidence of endothelial injury. It is concluded that the proliferative pulmonary changes that occur after the administration of butylated hydroxytoluene are a consequence of cell injury and necrosis. The reparative processes occur predominantly at the alveolar epithelium and interstitium with the production of fibrosis. The cellular hypertrophy and hyperplasia observed in this study account for the biochemical changes in pulmonary RNA and DNA that have been described previously.

Animals↗
PubMed1976

Biochemical paramters of BHT-induced cell growth in mouse lung.

Male mice of 7 different strains were injected i.p. with 400 mg/kg of butylated hydroxytoluene (BHT). 2 and 4 days later, the incorporation of thymidine into pulmonary DNA was significantly increased in all treated animals and this was accompanied by an increase in lung weight and pulmonary DNA. Thymidine kinase activity and DNA polymerase activity were enhanced in the lungs of BHT-treated animals and maximum activity of these enzymes appeared to precede maximum thymidine incorporation by 24 h. 3 days after BHT a good correlation was found between administered dose and thymidine kinase activity. Measuring the activity of this enzyme might serve as a convenient biochemical marker to follow and to quantitate BHT-produced cell proliferation in lung. The concentrations of cyclic AMP and the activity of adenylate cyclase were not altered by BHT on days 1-9 after administration. BHT produced also some dose-dependent, time-dependent increases in the activities of pulmonary 5'-nucleotidase and glucose-6-phosphate dehydrogenase (G6PDH), but had little effect on isocitric dehydrogenase (ICDH), pyruvate kinase (PK) and lactic dehydrogenase (LDH).

Animals↗
PubMed1976

Biochemical pathology of lung damage produced by chemicals.

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.

Animals↗
PubMed1975

Potentiation of the hepatotoxic responses to chemicals in alloxan-diabetic rats.

Alloxan diabetes enhances the hepatotoxic response of male rats to chloroform and 1, 1, 2-trichloroethane, but not to trichloroethylene nor 1, 1, 1-trichloroethane. Insulin treatment partially protects the animals against the alloxan-induced enhancement of chloroform hepatotoxicity. Alloxan diabetes also enhances the hepatotoxic response to galactosamine but not to beryllium nor alpha-naphthylisothiocyanate.

1-Naphthylisothiocyanate↗