Knebel J W, Aufderheide M, Emura M
Institute of Experimental Pathology, Hannover Medical School, Germany.
Toxicol Lett. 1994 Jun;72(1-3):65-72. doi: 10.1016/0378-4274(94)90011-6.
The cytotoxicity and frequencies of transformation induced by 5 environmental polycyclic aromatic hydrocarbons (PAH) in hamster (M3E3/C3) and rat (WRB K3) lung cells were compared. Both cell strains investigated here retain major metabolic characteristics of the target cells in vivo and are thus able to effectively metabolize, i.e. activate, PAH. Cytotoxic effects of the carcinogen were determined in colony-forming assays and the PAH tested induced dose-dependent cytotoxic responses in the M3E3/C3 and WRB cells. They could then be classified into strong and weak cytotoxicity. Compared to the hamster cell system, the WRB cells were generally shown to be more sensitive. The transforming capacity of the compounds was determined by a soft agar colony formation assay detecting cells with anchorage independency (AI). All PAH investigated induced transformation to AI growth in both cell systems. The transforming activity of the PAH, relative to benzo[a]pyrene (B[a]P) as a reference substance, was determined to facilitate their ranking. This order of transforming potency appears to be similar to that observed in animal studies.
比较了5种环境多环芳烃(PAH)在仓鼠(M3E3/C3)和大鼠(WRB K3)肺细胞中诱导的细胞毒性和转化频率。此处研究的两种细胞系保留了体内靶细胞的主要代谢特征,因此能够有效地代谢,即激活PAH。在集落形成试验中测定致癌物的细胞毒性作用,所测试的PAH在M3E3/C3和WRB细胞中诱导剂量依赖性细胞毒性反应。然后可将它们分为强细胞毒性和弱细胞毒性。与仓鼠细胞系统相比,WRB细胞通常表现出更高的敏感性。通过检测具有锚定非依赖性(AI)细胞的软琼脂集落形成试验来确定化合物的转化能力。所研究的所有PAH在两种细胞系统中均诱导向AI生长的转化。相对于作为参考物质的苯并[a]芘(B[a]P),测定PAH的转化活性以促进其排序。这种转化效力顺序似乎与在动物研究中观察到的相似。