32P-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 microm 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), 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 MDIV. In the lung, neither isocyanate adducts nor the arylamine adduct 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 10(10) nucleotides, for the three dose groups, respectively. The adduct co-chromatographed 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.
Vock
E H
EH
Institute of Toxicology, Swiss Federal Institute of Technology, Schwerzenbach, Switzerland.
Hoymann
H G
HG
Heinrich
U
U
Lutz
W K
WK
D000280:Administration, Inhalation; D000814:Aniline Compounds / Q000378:metabolism*; D000818:Animals; D002273:Carcinogens / Q000378:metabolism*; D018736:DNA Adducts / Q000032:analysis*; D005260:Female; D017953:Isocyanates / Q000378:metabolism*; D008297:Male; D009297:Nasal Mucosa / Q000378:metabolism*; D010761:Phosphorus Radioisotopes; D051381:Rats; D011916:Rats, Inbred F344; D017208:Rats, Wistar; D001559:Benzhydryl Compounds
D000814:Aniline Compounds; D002273:Carcinogens; D018736:DNA Adducts; D017953:Isocyanates; D010761:Phosphorus Radioisotopes; C005969:4,4'-diphenylmethane diisocyanate; D001559:Benzhydryl Compounds; C009505:4,4'-diaminodiphenylmethane