DNA adduct formation in human and rat mammary epithelium by N-hydroxy derivatives of 2-aminofluorene and 4-aminobiphenyl.
Primary cultures of rat mammary epithelium and the human mammary cell line MCF-12 were incubated with 10 microM N-formyl-, N-acetyl-, or N-propionyl-derivatives of N-hydroxy-2-aminofluorene (N-OH-AF) or N-formyl-, or N-acetyl derivatives of N-hydroxy-4-aminobiphenyl (N-OH-ABP), in the medium with or without 100 microM paraoxon, for 3 h. Carcinogen-DNA adducts in the nuclei were detected with an immunohistochemical method using polyclonal antibodies against N-(deoxyguano-8-yl)-2-aminofluorene and ABP-DNA adducts. The relative amounts of adducts per nucleus were determined by image analysis. After treatment, more than 90% of the cells that were attached on the coverslip were alive, as determined by the trypan blue exclusion. All carcinogens produced adducts in both human and rat cells. Adduct formation by the formyl, but not the acetyl or porpionyl, derivatives was inhibited up to 65% by paraoxon. These results demonstrate that both acetyl and propionyl derivatives are primarily activated by cytosolic acetyltransferases and the formyl derivatives may be equally activated by the acetyltransferases and microsomal carboxylesterases. Additionally, the results suggest that exposure to aromatic amines may be a risk factor for human breast cancer.
Debiec-Rychter
M
M
Department of Urology, State University of New York Health Science Center, Syracuse 13210, USA.
Tada
M
M
Poirier
M C
MC
Wang
C Y
CY
D000611:Aminobiphenyl Compounds / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001940:Breast / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D018736:DNA Adducts / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D005260:Female; D005449:Fluorenes / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008321:Mammary Glands, Animal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009153:Mutagens; D051381:Rats; D011916:Rats, Inbred F344
D000611:Aminobiphenyl Compounds; D018736:DNA Adducts; D005449:Fluorenes; D009153:Mutagens; C001368:N-hydroxy-2-aminofluorene; C014593:N-hydroxy-4-aminobiphenyl