The importance of short term exposure of C3H 10T12 cells to polycyclic hydrocarbons: Evidence for hydrocarbon-mediated anticarcinogenic activity

Abstract Since it has been shown that transformation frequencies (TF) of cultured mammalian cells exposed to polycyclic aromatic hydrocarbons (PAH) reach a maximum with increasing PAH concentration and then decline, we have examined TF in C3H 10T 1 2 CL8 ( 10T 1 2 ) cells as a function of an additional parameter of treatment, length of exposure. A 15-min exposure to either benzo[ a ]pyrene (BP) or 3-methylcholanthrene (3-MC), at concentrations ranging from 0.3 to 10 μg/ml, was sufficient to induce transformation suggesting that, in 10T 1 2 cells, non-induced enzymes of the cytochrome P -450 system are involved in the metabolic activation of PAH. At lower BP concentrations (0.3–1.25 μg/ml), TF generally increased with exposure time; at higher BP concentrations (2.5–10 μg/ml) maximal TF were achieved with 3 h of exposure. For 3-MC, maximal TF occurred at 0.5–1 h with a concentration of 10 μg/ml and at 1–6 h with lower concentrations. Moreover, low TF were obtained after 12-h and 24-h exposures to 10 μg/ml BP or 3-MC. These results show that TF depend on both the length of exposure and concentration of PAH. Since both BP and 3-MC are extensively metabolized to polyoxygenated derivatives and conjugates, we suggest that certain metabolites may be anticarcinogenic or antipromoting agents. The identities of such metabolites are yet to be determined.