COMPARISON OF RAT HEPATOCYTE AND DIFFERENTIATED HEPATOMA-CELL LINE CULTURES AS BIO-INDICATORS OF CYP 1A1 INDUCERS IN URBAN AIR

Cytochrome P450 1A1 (CYP1A1) enzymatic activity was evaluated in cultu red liver cells, and taken as a biological indicator of the presence o f inducers of this isoform in urban airborne particulate matter fracti on samples. It is known that CYP1A1 inducers can play an important rol e in the risk of mutagenesis and carcinogenesis by environmental pollu tion. Aromatic polycyclic hydrocarbons (PAH) from urban air were colle cted in the city of Genoa (Italy) at two sites on two different days o f the year. The objective of the study was to compare the inducibility of cultured rat hepatocytes with that of MH1C1 and FaO rat hepatoma c ell lines after exposure to a PAH mixture and to a standard compound, such as benzo[b]fluoranthene (B[b]F). Cytotoxic effects of the tested concentrations were evaluated by means of ,5,-dimenthylthyazol-2-yl]-2 ,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase release (LDH) tests, the potency of inducers by ethoxyresorufin-O-deethylase (EROD) assay. The results were in agreement in the three cellular syst ems: after exposure to the PAH mixture, an induction at low concentrat ions was observed; whereas no induction, but rather a decrease in acti vity was shown at higher concentrations; instead, the exposure to pure B[b]F showed a dose-response relationship in all cells, even at the h ighest doses. Such a difference between the toxicity of the complex mi xture and that of the pure compound could be ascribed to the presence of drug metabolism inhibitors in the mixture, or to interactions betwe en the original components and their metabolites. The finding that the cell lines responded to the CYP1A1 induction in a very efficient way gives further proof of the applicability of this system to environment al biomonitoring.