TRICHLOROETHYLENE-INDUCED MOUSE LUNG-TUMORS - STUDIES OF THE MODE OF ACTION AND COMPARISONS BETWEEN SPECIES

CD-1 mice exposed to 450 ppm trichloroethylene, 6 hr/day, 5 days/week, for 2 weeks showed a marked vacuolation of lung Clara cells after the first exposure of each week and a marked increase in cell division af ter the last exposure of each week, The damage seen in mouse lung Clar a cells is caused by an accumulation of chloral resulting from high ra tes of metabolism of trichloroethylene but poor clearance of chloral t o trichloroethanol and its glucuronide. The activity and distribution of the key metabolizing enzymes in this pathway have been compared in mouse, rat, and human lung. While mouse lung microsomal fractions were able to metabolize trichloroethylene to chloral at significant rates, the rate in rat lung was 23-fold lower and a rate could not be detect ed in human lung microsomes at all, Immunolocalization of cytochrome P 450IIE1 in lung sections revealed high concentrations in mouse lung Cl ara cells with lesser amounts in type II cells. Lower levels of enzyme could be detected in Clara cells of rat lung, but not at all in human lung sections. Western blots of lung tissues from the three species a nd of mouse lung Clara cells were entirely consistent with these obser vations, Consequently, it is highly unlikely that humans exposed to tr ichloroethylene are at risk from the lung damage/cell proliferation me chanism that is believed to lead to the development of tumors in the m ouse lung. (C) 1997 Society of Toxicology.