Metabolism of [3H]benzo[a]pyrene by cultured human bronchus and cultured human pulmonary alveolar macrophages
Autrup, H; Harris, CC; Stoner, GD; Selkirk, JK; Schafer, PW; Trump, BF
HERO ID
59970
Reference Type
Journal Article
Year
1978
Language
English
PMID
| HERO ID | 59970 |
|---|---|
| In Press | No |
| Year | 1978 |
| Title | Metabolism of [3H]benzo[a]pyrene by cultured human bronchus and cultured human pulmonary alveolar macrophages |
| Authors | Autrup, H; Harris, CC; Stoner, GD; Selkirk, JK; Schafer, PW; Trump, BF |
| Journal | Laboratory Investigation |
| Volume | 38 |
| Issue | 3 |
| Page Numbers | 217-224 |
| Abstract | HEEP COPYRIGHT: BIOL ABS. The metabolism of the carcinogen (3H)benzo(a)pyrene by cultured human bronchial epithelium and cultured pulmonary alveolar macrophages from the same donor was studied. Explants of bronchus were prepared from surgical and autopsy specimens, and human pulmonary alveolar macrophages were isolated from peripheral lung by trypsinization and differential adhesion to plastic tissue culture dishes. After 7 days in culture the bronchus explant and pulmonary alveolar macrophages were exposed to (3H)benzo(a)pyrene, and binding to cellular macromolecules was studied. Aryl hydrocarbon hydroxylase activity was determined by the release of 3H water into the culture medium from metabolized (3H)benzo(a)pyrene. Variation in the binding level of benzo(a)pyrene to DNA and protein in pulmonary alveolar macrophages from different individuals showed 9- and 33-fold interindividual variation, respectively. The metabolism of benzo(a)pyrene was further investigated in macrophages. Binding of benzo(a)pyrene to macromolecules and aryl hydrocarbon hydroxylase activity were dependent on the length of time the explant was in culture and length of exposure to benzo(a)pyrene. Pretreatment of macrophages with benz(a)anthracene increased the binding level of benzo(a)pyrene and aryl hydrocarbon hydroxylase activity. When coincubated with benzo(a)pyrene, cycloheximide, 7,8-benzoflavone or actinomycin D reduced both the level of binding and activity of aryl hydrocarbon hydroxylase. When macrophage cultures were maintained at pO2 greater than atmospheric air, an increase in binding level and enzyme activity was found. The major metabolites of benzo(a)pyrene formed by macrophages were 7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene, (5-25% of total metabolites) 9,10-dihydroxy-9,10-dihydrobenzo(a)pyrene (16-39%) and 2 distinct peaks containing unidentified polar metabolites. A negative correction (r = -0.58; P 0.05) between binding of benzo(a)pyrene to protein and aryl hydrocarbon hydroxylase exists in pulmonary macrophages, but no correlation between data from bronchus and macrophages was found. |
| Pmid | 633846 |
| Is Certified Translation | No |
| Dupe Override | 59970 |
| Comments | 3 in title is a superscript.Lab. Invest. 38: 217-224. |
| Is Public | Yes |
| Language Text | English |
| Is Qa | No |