Mitchell C E, Thomassen D G
Inhalation Toxicology Research Institute, Lovelace Biomedical and Environmental Research Institute, Albuquerque, NM 87185.
Carcinogenesis. 1990 Jan;11(1):155-8. doi: 10.1093/carcin/11.1.155.
Four nitropolycyclic aromatic hydrocarbons (NPAHs) were investigated for their cytotoxic effects on rat tracheal epithelial (RTE) cells. 6-Nitrochrysene (6-NC), 1,6-dinitropyrene (1,6-DNP), 1-nitropyrene (1-NP) and 4-nitropyrene (4-NP) induced dose-dependent decreases in the relative colony-forming efficiency (RCFE) of RTE cells. The compounds could be separated into two groups based on their cytotoxic potencies, a group that displayed high cytotoxic effects (6-NC and 1,6-DNP), and a group that displayed low cytotoxic effects (1-NP and 4-NP). The most cytotoxic compound was 6-NC, with an ED50 of 0.13 microM, followed by 1,6-DNP, 4-NP and 1-NP with ED50s of 1.25, 8.9 and 9.1 microM, respectively. The most cytotoxic compound (6-NC) and one of the components with low cytotoxicity (1-NP) were assayed for their ability to induce preneoplastic transformation of RTE cells using equally toxic doses of both compounds. The frequencies of transformation induced by 6-NC in cells isolated from control animals or from animals pretreated with 3-methylcholanthrene (3-MC) were 8.4 X 10(-3) and 21.4 X 10(-3), respectively. 1-NP did not induce cell transformation. Equally toxic doses of the direct acting carcinogen N-methyl-N'-nitro-N-nitrosoguanidine, used as a positive control, induced transformation frequencies of 8.7 X 10(-3) and 6.4 X 10(-3) in cells isolated from control animals or from animals pretreated with 3-MC, respectively. These studies show that RTE cells have the metabolic capacity to activate NPAHs to toxic metabolites; thus, the RTE system should be very useful for evaluating the potential toxic effects of this ubiquitous class of airborne pollutants. In addition, the observed differences in cellular toxicity and transformation capabilities of 6-NC and 1-NP were consistent with the results of other studies that demonstrated the greater potency for induction of tumors in animals of 6-NC relative to 1-NP.
研究了四种硝基多环芳烃（NPAHs）对大鼠气管上皮（RTE）细胞的细胞毒性作用。6-硝基 Chrysene（6-NC）、1,6-二硝基芘（1,6-DNP）、1-硝基芘（1-NP）和 4-硝基芘（4-NP）均诱导 RTE 细胞的相对集落形成效率（RCFE）呈剂量依赖性下降。根据细胞毒性强度，这些化合物可分为两组，一组具有高细胞毒性（6-NC 和 1,6-DNP），另一组具有低细胞毒性（1-NP 和 4-NP）。细胞毒性最强的化合物是 6-NC，其半数有效剂量（ED50）为 0.13μM，其次是 1,6-DNP、4-NP 和 1-NP，其 ED50 分别为 1.25、8.9 和 9.1μM。使用两种化合物的同等毒性剂量，对细胞毒性最强的化合物（6-NC）和低细胞毒性成分之一（1-NP）诱导 RTE 细胞发生癌前转化的能力进行了测定。6-NC 在从对照动物或经 3-甲基胆蒽（3-MC）预处理的动物分离的细胞中诱导的转化频率分别为 8.4×10⁻³和 21.4×10⁻³。1-NP 未诱导细胞转化。用作阳性对照的直接作用致癌物 N-甲基-N'-硝基-N-亚硝基胍的同等毒性剂量，在从对照动物或经 3-MC 预处理的动物分离的细胞中诱导的转化频率分别为 8.7×10⁻³和 6.4×10⁻³。这些研究表明，RTE 细胞具有将 NPAHs 激活为有毒代谢物的代谢能力；因此，RTE 系统对于评估这类普遍存在的空气传播污染物的潜在毒性作用应该非常有用。此外，观察到的 6-NC 和 1-NP 在细胞毒性和转化能力方面的差异与其他研究结果一致，这些研究表明，相对于 1-NP，6-NC 在动物中诱导肿瘤的能力更强。
