The importance of short term exposure of C3H 10T1/2 cells to polycyclic hydrocarbons: evidence for hydrocarbon-mediated anticarcinogenic activity.
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 10T1/2 CL8 (10T1/2) cells as a function of an additional parameter of treatment, length of exposure. A 15-min exposure to either benzo[alpha]pyrene (BP) or 3-methylcholanthrene (3-MC), at concentrations ranging from 0.3 to 10 micrograms/ml, was sufficient to induce transformation suggesting that in 10T1/2 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 micrograms/ml), TF generally increased with exposure time; at higher BP concentrations (2.5-10 micrograms/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 micrograms/ml and at 1-6 h with lower concentrations. Moreover, low TF were obtained after 12-h and 24-h exposures to 10 micrograms/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.
D000818:Animals; D001580:Benzopyrenes / Q000378:metabolism*; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D008658:Inactivation, Metabolic; D008748:Methylcholanthrene / Q000378:metabolism*; D051379:Mice; D013997:Time Factors
D001580:Benzopyrenes; D008748:Methylcholanthrene