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DNA adduct formation in human and rat mammary epithelium by N-hydroxy derivatives of 2-aminofluorene and 4-aminobiphenyl

✍ Scribed by Maria Debiec-Rychter; Mariko Tada; Miriam C. Poirier; Ching Y. Wang


Publisher
John Wiley and Sons
Year
1998
Tongue
English
Weight
23 KB
Volume
18
Category
Article
ISSN
0270-3211

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✦ Synopsis


Primary cultures of rat mammary epithelium and the human mammary cell line MCF-12 were incubated with 10 µM N-formyl-, N-acetyl-, or N-propionyl-derivatives of N-hydroxy-2-aminofluorene (N-OH-AF) or N-formyl-, or N-acetyl derivatives of Nhydroxy-4-aminobiphenyl (N-OH-ABP), in the medium with or without 100 µM 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


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