Influence of sulfur dioxide on metabolism and distribution of benzo[a]pyrene in isolated perfused rabbit lung.

An isolated perfused lung [IPL) preparation was used to investigate the effects of SO2 (1-2 ppm) on the metabolism of benzo[a]pyrene (BaP), a ubiquitous potent carcinogen that has been associated with the increased incidence of a human bronchiogenic carcinoma in occupational and urban populations. [14C]BaP, with and without crude air particulate (CAP), was administered intratracheally to the IPL in conjunction with SO2 or after pretreatment of the whole animal with SO2. Metabolites were isolated from serial blood samples up to 3 h after the administration of [14C]BaP to the IPL. Metabolites were also isolated from lung tissue, washout fluid, macrophage, and trachea and bronchi at the end of the perfusion at 180 min. Patterns of BaP metabolites were determined by thin-layer and high-performance liquid chromatography and scintillation counting. SO2 given in conjunction with BaP on the IPL or given to the whole animal followed by BaP on the IPL, in comparison with BaP only on the IPL, resulted in a twofold increase in the total rate of appearance of metabolites of BaP in the blood with changes in the metabolic pattern. SO2 given in conjunction with BaP and CAP on the IPL, in comparison with BaP plus SO2 on the IPL, resulted in a threefold decrease in the total rate of appearance of metabolites of BaP in the blood with changes in the metabolic pattern.