Ball L M, Plummer J L, Smith B R, Bend J R
Med Biol. 1979 Oct;57(5):298-305.
The isolated perfused rabbit lung metabolised 7--11 % of 20 mumol of [14C]-benzo(a)pyrene added in the perfusion medium in 1 h. The major metabolite formed was 3-hydroxybenzo(a)pyrene, both free (30--40 % of the total metabolites) and conjugated (4 % of total metabolites). Quinones comprised 15 % of the total and metabolism at the 9, 10 position accounted for a further 10 %. Forty per cent of the water-soluble metabolites was chromatographically identical to the glutathione conjugate of benzo(a)pyrene 4,5-oxide. Sulphate and glucuronide conjugates were formed in small but detectable amounts, principally from phenols, but also from dihydrodiols. After 1 h the more water-soluble conjugates had diffused from the lung into the perfusion medium, but the majority (60--90 %) of the metabolic products were still concentrated within the lung. The lung's limited ability to conjugate its major metabolites of benzo(a)pyrene with sulphuric or glucuronic acid, coupled with slow elimination of the products formed, particularly dihydrodiols may contribute to the susceptibility of this organ to polycyclic aromatic hydrocarbon-induced carcinogenesis.
离体灌注的兔肺在1小时内代谢了灌注液中添加的20 μmol [¹⁴C] -苯并(a)芘的7% - 11%。形成的主要代谢产物是3 -羟基苯并(a)芘，包括游离形式（占总代谢产物的30% - 40%）和结合形式（占总代谢产物的4%）。醌类占总代谢产物的15%，9、10位的代谢占另外10%。40%的水溶性代谢产物在色谱上与苯并(a)芘4,5 -氧化物的谷胱甘肽结合物相同。硫酸盐和葡萄糖醛酸结合物的生成量虽少但可检测到，主要来自酚类，也来自二氢二醇。1小时后，水溶性更强的结合物已从肺扩散到灌注液中，但大部分（60% - 90%）代谢产物仍集中在肺内。肺将苯并(a)芘的主要代谢产物与硫酸或葡萄糖醛酸结合的能力有限，加上生成产物的消除缓慢，尤其是二氢二醇，可能导致该器官对多环芳烃诱导的致癌作用敏感。
