Cohen G M, Mehta R, Meredith-Brown M
Int J Cancer. 1979 Aug;24(2):129-33. doi: 10.1002/ijc.2910240202.
A very large variation (44-fold) was observed in the ability of short-term organ cultures of peripheral lung tissue from lung-cancer patients to metabolize the environmental carcinogen benzo(alpha)pyrene to organic solvent-soluble metabolites. The amounts of benzo(alpha)pyrene (2 microM) metabolized ranged from little (1%) to almost total (96.2%) metabolism within 24 h of culture. Previous work by Kellerman et al. (1973) has suggested a relationship between susceptibility to lung cancer and the indicibility of aryl hydrocarbon hydroxylase activity in cultured human lymphocytes. The metabolic fate of carcinogenic polycyclic aromatic hydrocarbons in the respiratory tract in vivo is undoubtedly more closely mimicked by short-term organ culture of human lung than by cultured lymphocytes. Thus the very wide interindividual variation observed in pulmonary metabolism of benzo(alpha)pyrene in this study and the large variations in covalent binding to human bronchial DNA observed by Harris et al. (1976) strongly suggest that there may be little basis for screening humans for variations in lymphocyte aryl hydrocarbon hydroxylase activity as a means of assessing their susceptibility to lung cancer.
在肺癌患者外周肺组织短期器官培养物代谢环境致癌物苯并（α）芘生成有机溶剂可溶性代谢产物的能力方面，观察到了非常大的差异（44倍）。在培养24小时内，苯并（α）芘（2微摩尔）的代谢量从极少（1%）到几乎完全（96.2%）代谢不等。凯勒曼等人（1973年）之前的研究表明，对肺癌的易感性与培养的人淋巴细胞中芳烃羟化酶活性的诱导性之间存在关联。与培养的淋巴细胞相比，人肺的短期器官培养无疑更能紧密模拟体内呼吸道中致癌多环芳烃的代谢命运。因此，本研究中观察到的苯并（α）芘肺部代谢的个体间差异极大，以及哈里斯等人（1976年）观察到的与人类支气管DNA共价结合的巨大差异，强烈表明，作为评估人类对肺癌易感性的一种手段，通过筛查淋巴细胞芳烃羟化酶活性的差异来筛选人类可能几乎没有依据。
