Wiersma D A, Braselton W E, Roth R A
Chem Biol Interact. 1983 Jan;43(1):1-15. doi: 10.1016/0009-2797(83)90101-1.
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.
为了研究血流以及底物输送对肺代谢外来化合物能力的影响，在以低流量（10毫升/分钟）和高流量（45毫升/分钟）灌注的对照大鼠和经3-甲基胆蒽（3-MC）预处理的大鼠的离体肺中，监测循环中[3H]苯并[a]芘（[3H]B[a]P）的消失以及B[a]P代谢产物的出现。增加流量或3-MC预处理会加速灌注培养基储库中B[a]P的消失，并提高总代谢产物的出现速率。然而，这些操作以不同方式影响培养基中单个代谢产物的出现。例如，在对照大鼠的肺中，增加流量会显著提高灌注培养基中7,8-二氢二醇（7,8-二羟基-7,8-二氢-B[a]P）（7,8-DHD）的出现速率，而对B[a]P-1,6-醌的影响最小。此外，增加流量会增加对照大鼠肺组织在灌注期末一些B[a]P代谢产物的浓度，如4,5-二氢二醇（4,5-二羟基-4,5-二氢-B[a]P）（4,5-DHD），但对经3-MC预处理的大鼠肺中这些代谢产物的浓度影响不大。结果表明，血流以及3-MC预处理可能会改变外来化合物的代谢速率以及完整肺产生的代谢产物的时间分布。
