cytochalasin-b and Pulmonary-Fibrosis

We studied micronucleus frequencies in former German uranium miners of the Wismut SDAG (Sowjetisch-Deutsche Aktiengesellschaft). Various other groups were analyzed for comparison (individuals with lung tumors or lung fibrosis, controls). We had shown previously that micronucleus frequencies were not different among the various groups. Differences were observed, however, when centromere-positive and -negative micronuclei were distinguished. In the analyses presented here, we looked for the effects of smoking habits, alcohol consumption, vitamin uptake, chronic diseases, allergies, doing sports, gamma-GT (gamma-glutamyltranspeptidase), lymphocyte numbers, CEA (carcinoembryonic antigen), X-ray diagnostics, computer tomographies, and scintigraphies. With the exception of more than one scintigraphy carried out during the last four months before micronucleus analysis, none of the factors mentioned above significantly affected micronucleus numbers. One result deserves specific attention: individuals with low percentages of binucleated lymphocytes after in vitro cytochalasin B exposure showed higher micronucleus frequencies than those individuals with high percentages of binucleated cells. The same result was obtained for various other populations that we monitored in the past.

Topics: Alcohol Drinking; Alpha Particles; Cell Nucleus; Centromere; Chromosomal Instability; Cytochalasin B; Dose-Response Relationship, Radiation; Gamma Rays; Germany; Life Style; Lung Neoplasms; Lymphocytes; Micronucleus Tests; Mining; Occupational Diseases; Occupational Exposure; Pulmonary Fibrosis; Radionuclide Imaging; Radon; Risk Factors; Smoking; Time Factors; Uranium

A single endotracheal administration of bleomycin causes pulmonary fibrosis in several animal species. In view of the functional deficits in neutrophil function as a result of the beige mouse (bg/bg) mutation, its effect on bleomycin-induced pulmonary fibrosis was examined to evaluate the role of the neutrophil in such a response. Neutrophils from beige mice showed a selective defect in the ability to degranulate in response to cytochalasin B and formyl-methionyl-leucyl-phenylalanine, without impairing their ability to produce superoxide anion and H2O2 in response to the same stimuli as well as phorbol myristate acetate. Despite this functional deficit, beige mice responded more intensely to bleomycin than did their heterozygote controls at both 2 wk and 1 month after drug instillation, as assessed by both lung collagen and deposition. This suggests that the inability to mobilize hydrolytic enzymes has no effect on the ability to mount a fibrogenic response, and it would even be detrimental by enhancing such a response caused by decreased connective tissue catabolism as a consequence of the inability to release the granule enzymes to the extracellular space.

Topics: Animals; Bleomycin; Collagen; Cytochalasin B; Dose-Response Relationship, Drug; Female; Hydroxyproline; Mice; Mice, Mutant Strains; N-Formylmethionine; N-Formylmethionine Leucyl-Phenylalanine; Neutrophils; Oligopeptides; Pulmonary Fibrosis