Metabolism of 2-acetylaminofluorene by clara cells,type II cells and alveolar macrophages isolated from rabbit lung,and use of a new chamber incubation mutagenicity test system |
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Authors: | Tore Aune Theodora R Devereux Kristi Tveito |
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Institution: | (1) Department of Toxicology, National Institute of Public Health, Oslo, Norway;(2) National Institute of Environmental Health Sciences, National Institutes of Health, Laboratory of Pharmacology, Research Triangle Park, NC;(3) Department of Toxicology, National Institute of Public Health, Geitmyrsveien 75, 0462 Oslo, Norway |
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Abstract: | Clara cells, alveolar type II cells and pulmonary alveolar macrophages (PAM) were isolated in high yield from rabbit lung. The purity of the cell fractions was 80–90%, 98% and above 99%, respectively. Cytochrome P-450 total content was determined in microsomes from freshly prepared cells. The Clara cells contained significantly more cytochrome P-450 than was found in whole lung microsomes. Furthermore, the cytochrome content of the Clara cells was 2 -fold higher than in the type II cells and 4 -fold higher than in the macrophages. 2-aminofluorene (AF) was the major metabolite in all preparations when intact cells were incubated with 2-acetylaminofuorene (AAF). The PAMs produced AF in the highest rates, while the Clara cells showed the largest rates of cytochrome P-450-dependent, ring hydroxylation of AAF. Mutagenic activation of AAF by isolated lung cells was assayed with a chamber-incubation method. The Clara cells were far more active than the type II cells in this respect, while the macrophages were inactive.Abbreviations AAF
2-acetylaminofluorene
- AF
2-aminofluorene
- DMSO
dimethyl sulfoxide
- NBT
nitro blue tetrazolium
- 7-OH-AAF
7-hydroxy-AAF
- 9-OH-AAF
9-hydroxy-AAF |
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Keywords: | AAF isolated rabbit lung cells metabolism mutagenic activation |
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