The influence of flow on the metabolism of perfused benzo[a]pyrene by isolated rat lung.
In order to investigate the influence of flow and, thus, substrate delivery, on the ability of lung to metabolize foreign compounds, the disappearance of circulating [3H]benzo[a]pyrene ([3H]B[a]P) and the appearance of B[a]P metabolites was monitored in isolated rat lungs from control and 3-methylcholanthrene (3-MC) pretreated rats perfused at low (10 ml/min) and high (45 ml/min) flows. Increasing the flow or 3-MC pretreatment hastened the disappearance of B[a]P from the perfusion medium reservoir and increased the rate of appearance of total metabolites. However, these manipulations affected the appearance of individual metabolites in the medium in different ways. For example, in lungs from control rats the rate of appearance of 7,8-dihydrodiol (7,8-dihydroxy-7,8-dihydro-B[a]P) (7,8-DHD) in the perfusion medium was markedly increased by increasing flow while that of B[a]P-1,6-quinone was minimally affected. In addition, increasing flow increased the concentration of some B[a]P metabolites, such as 4,5-dihydrodiol (4,5-dihydroxy-4,5-dihydro-B[a]P) (4,5-DHD) in the lung tissue of control rats at the end of the perfusion period, but did not effect much change in the concentration of these metabolites in lungs from 3-MC-pretreated rats. The results show that flow, as well as 3-MC pretreatment, may alter the rate at which metabolism of foreign compounds occurs and the temporal profile of metabolites produced by the intact lung.
D000818:Animals; D001564:Benzo(a)pyrene; D001580:Benzopyrenes / Q000008:administration & dosage / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004101:Dihydroxydihydrobenzopyrenes; D004790:Enzyme Induction; D008168:Lung / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains
D001580:Benzopyrenes; D004101:Dihydroxydihydrobenzopyrenes; C017228:benzo(a)pyrene 7,8-dihydrodiol; C015813:4,5-dihydroxy-4,5-dihydrobenzo(a)pyrene; D001564:Benzo(a)pyrene