GENETIC MODELING OF SUSCEPTIBILITY TO NITROGEN DIOXIDE-INDUCED LUNG INJURY IN MICE

We investigated the mode of inheritance of susceptibility to nitrogen dioxide (NO2)-induced lung injury in inbred mice. Susceptible C57BL/6J (B6) and resistant C3H/HeJ (C3) mice, as well as F-1, F-2, and backcr oss (BX) populations derived from them, were exposed to 15 parts per m illion NO2 for 3 h. Six hours after exposure, animals were lavaged, an d differential cell counts and cell viability (cytotoxicity) were meas ured. Statistically significant (P < 0.05) differences in numbers of l avageable macrophages, epithelial cells, and dead cells were found bet ween inbred strains. Distributions of cellular responses in F-1 progen y overlapped both progenitors, and mean responses were intermediate. I n C3:BX progeny, ranges of responses to NO2 closely resembled C3 mice, and means were not significantly different between populations. Range s of cellular responses to NO2 in B6:BX and intercross progeny overlap ped both progenitors; mean responses of both populations were intermed iate to progenitors. Segregation analyses tested goodness of fit of ph enotyping data with various inheritance models, and the highest likeli hood for each cell response to NO2 was for the hypothesis two-unlinked loci general. We conclude that there are likely two major unlinked ge nes that account for differential susceptibility to acute NO2 exposure . The chromosomal location of the genes is not known.