32P-Postlabeling of a DNA adduct derived from 4,4'-methylenedianiline in the olfactory epithelium of rats exposed by inhalation to 4,4'methylenephenyl diisocyanate
Tissues obtained from female Wistarrats exposed to a 0.9 µm aerosol of 4,4'-methylenediphenyl diisocyanate (MDI) for 17 h per day, 5 days per week, for one year at levels of 0, 0.3, 0.7 and 2.0 mg /m3, were analyzed for DNA adducts. A 32P-postlabeling method was used to detect (i) adducts formed by the reaction of the isocyanate group(s) of MDI with DNA; and a 32P-postlabeling method was adapted to detect (ii) a DNA adduct formed by 4,4'-methylenedianiline (MDA), a hydrolysis/decarboxylation product of MDI. In the lung, neither isocyanate adducts nor the arylamine aducts were detectable. The same negative result was seen in the liver, the bladder, the kidney, the respiratory epithelium and in peripheral lymphocytes. In the olfactory epithelium, on the other hand, the arylamine-derived DNA adduct was detected at the very low levels of 5, 9 and 10 adduct-nucleotides per 1010 nucleotides for the three dose groups, respectively. The adduct cochromatographed with the one formed in the liver of rats after oral gavage of MDA. The results are discussed in terms of the importance of genotoxic versus nongenotoxic aspects of carcinogenesis.