IN-VITRO MODULATION OF THE P450 ACTIVITIES OF HAMSTER AND HUMAN LUNG SLICES

The respiratory tract is a portal of entry for many environmental chem icals. The respiratory tract plays an important role in the detoxifica tion or metabolic activation of these chemicals, e.g., via cytochrome P450 enzymes. Alterations in the capabilities of these enzymes to meta bolize inhaled compounds can, therefore, affect the toxicity of the ch emicals. The pulmonary cytochrome P450 activity has been studied in ma ny species, but relatively little is known about this activity in the human lung tissue. In this limited study, we have investigated the pos sibility of modulating in vitro the P450 activity in lung slices from hamsters and humans. The alkoxyresorufin-O-dealkylase activity was mea sured in the S9 fraction of lung slices incubated for 24 h with 10(6) mol/L 20-methylcholanthrene (3MC) or beta-naphthoflavone (PN). The eth oxyresorufin-O-deethylase (EROD) activity was increased by 3MC and PN in lung slices of both species. The benzyloxyresorufin-O-deethylase (B ROD) activity was decreased after incubation with 3MC but increased wi th PN. These data show that in vitro modulation in lung slices is feas ible, although technical improvement is still needed, particularly in relation to the viability of the slices.