methylnitronitrosoguanidine and 4-nitropyrene

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.

Topics: Animals; Carcinogens; Cell Survival; Cell Transformation, Neoplastic; Cells, Cultured; Chrysenes; Dose-Response Relationship, Drug; Epithelial Cells; Epithelium; Male; Methylnitronitrosoguanidine; Polycyclic Compounds; Pyrenes; Rats; Rats, Inbred F344; Trachea