[Studies on the metabolism of benzo(a)pyren in alveolar-macrophages. I. Uptake of benzo(a)pyrene and induction of benzo(a)pyrene hydroxylase (author's transl)].
Alveolar macrophages play a significant role in the elimination of inhaled foreign compounds and particles from the lung. The question arises, if alveolar macrophages participate in the detoxification or activation of environmental carcinogenic compounds. In the first communication on this subject we describe experiments concerning the uptake of benzo(a)pyrene and the activity of the metobolizing enzymes. The alveolar macrophages are obtained by lung lavage from guinea pigs (Fig. 1,2,3). The cells are grown in monolayers in petri dishes or on the surface of cover slips or glass-vials. The uptake of benzo(a)pyrene in alveolar macrophages is measured by a microfluorimetric method in single cells and by using labelled substrate. The results obtained by both methods indicate that the uptake is terminated between 1-2 h (Fig. 4, 5). The kinetics of uptake and elimination (Fig. 8, 9). are influenced by the concentration of serum (Fig. 6) and benzo(a) pyrene (Fig. 7) in the medium. Two mechanism for the uptake in the alveolar macrophages are discussed: diffusion and pinocytose. The activity of the metabolizing enzymes (benzo(a)pyrene hydroxylase, aryl hydrocarbon hydroxylase)increases during incubation with benzo(a)pyrene (Fig. 10, 11) and is dependant on the concentration of benzo(a)pyrene in the growth medium (Fig. 12). The enzyme activity is inducible also by other polycyclic hydrocarbons (Tab. 1). The induction is inhibited by actinomycin D and cycloheximid (Tab. 2). The activity of the enzymes in guinea pig alveolar macrophages is comparable to the activity in leucocytes and alveolar-macrophages from humans (Tab. 3, 4).
D000818:Animals; D001579:Benzopyrene Hydroxylase / Q000378:metabolism*; D001580:Benzopyrenes / Q000378:metabolism*; D001798:Blood Proteins; D002478:Cells, Cultured; D003470:Culture Media; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004790:Enzyme Induction; D005470:Fluorometry; D006168:Guinea Pigs; D008264:Macrophages / Q000201:enzymology / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000166:cytology*
D001580:Benzopyrenes; D001798:Blood Proteins; D003470:Culture Media; D003609:Dactinomycin; D003513:Cycloheximide; D006899:Mixed Function Oxygenases; D001579:Benzopyrene Hydroxylase
Untersuchungen iiber den Metabolismus von Benzo(a)pyren in Alveolarmakrophagen. I. Aufnahme von Benzo(a)pyren and Induktion der Benzo(a)pyren-Hydroxylase