P-32 POSTLABELING OF A DNA ADDUCT DERIVED FROM 4,4'-METHYLENEDIANILINE, IN THE OLFACTORY EPITHELIUM OF RATS EXPOSED BY INHALATION TO 4,4'-METHYLENEDIPHENYL DIISOCYANATE

Tissues obtained from female Wistar rats exposed to a 0.9 mu m 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/m(3), wer e analyzed for DNA adducts, A P-32-postlabeling method was used to det ect (i), adducts formed by the reaction of the isocyanate group(s) of MDI with DNA; and a P-32-postlabeIing 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 adduct s nor the arylamine adduct were detectable, The same negative result w as seen in the liver, the bladder, the kidney, the respiratory epithel ium and in peripheral lymphocytes, In the olfactory epithelium, on the other hand, the arylamine-derived DNA adduct was detected, at the ver y low levels of 5, 9 and 10 adduct-nucleotides per 10(10) nucleotides, for the three dose groups, respectively, The adduct cochromatographed with the one formed in the liver of rats after oral gavage of MDA, Th e results are discussed in terms of the importance of genotoxic versus nongenotoxic aspects of carcinogenesis.