Cell-mediated mutagenesis and tumor-initiating activity of the ubiquitous polycyclic hydrocarbon, cyclopenta[c,d]pyrene

The ubiquitous polycyclic aromatic hydrocarbon (PAH), cyclopenta[c,d]pyrene (CPP), was tested to determine its mutagenicity for 6-thioguanine and ouabain resistance in Chinese hamster V79 cells and its tumor-initiating activity in the skin of the tumor susceptible Sencar mice. The potent carcinogen/mutagen, benzo[a]pyrene (BP), was included for comparison. Inasmuch as V79 cells do not metabolize PAHs, mutagenesis was tested both in the presence and in the absence of X-irradiated golden hamster embryo fibroblasts capable of metabolizing PAH. Neither CPP nor BP showed mutagenicity for V79 cells in the absence of the embryo cells. In the presence of these cells (in the cell-mediated assay) both PAHs elicited, in a dose dependent manner, a cytotoxic and mutagenic response in V79 cells. CPP was however less active than BP in inducing both of these responses. At the optimal expression time and at the dose range of 0.1-1 μg/ml, CPP induced 2-8 6-thioguanine resistant mutants per 10⁵ colony forming cells compared to 9-50 mutants induced by BP. Similarly, these doses of CPP induced 1-9 ouabain resistant mutants per 10⁶ colony forming cells compared to 7-75 mutants induced by BP. CPP was also active in initiating skin tumors in a dose dependent manner in the Sencar mice yielding tumors in ∼60% of the mice at 200 μg, the highest dose tested. BP was more efficient in tumor initiation and yielded a similar response with 10 μg. These results indicate that CPP and BP elicit, in the cell mediated assay, a mutagenic response similar to the activity of these PAH in the skin of Sencar mice.