PMID: 6400924Oct 1, 1984Paper

Modulation of genotoxic and cytotoxic effects of aromatic amines in monolayers of rat hepatocytes

Cell Biology and Toxicology
J A Holme, E Søderlund

Abstract

Cultured rat hepatocytes exposed to 2-acetylaminofluorene (AAF), 2-aminofluorene (AF) or N-hydroxy-2-acetylaminofluorene (N-OH-AFF) for 3 hrs resulted in an increase in DNA repair measured as unscheduled DNA synthesis, with N-OH-AAF greater than AAF greater than AF. Cytotoxic effects were only seen with N-OH-AAF above 10(-6) M. alpha-Naphthoflavone increased the unscheduled DNA synthesis and cytotoxic effects of N-OH-AAF, whereas it decreased DNA repair and the covalent binding of AAF to cellular proteins. In contrast, very little effects of paraoxon were seen on the repair synthesis elicited by AAF, AF or N-OH-AAF. The addition of ascorbate reduced the covalent binding of AAF, the DNA repair synthesis caused by AAF and N-OH-AAF, and the cytotoxic effects of N-OH-AAF. The addition of pentachlorophenol or salicylamide all resulted in similar effects as ascorbate, through reduction of sulfation. Galactosamine, an inhibitor of glucuronidation, and the nucleophile GSH caused no or only minor effects of the activation of AAF, AF or N-OH-AAF as judged from the endpoints tested. These results are consistent with an arylnitrenium ion, a sulfate ester or a free radical as the arylamine metabolite causing cellular DNA damage, whereas the...Continue Reading

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Citations

Jan 1, 1989·Cell Biology and Toxicology·F Denizeau, M Marion
Jan 1, 1985·Cell Biology and Toxicology·F DenizeauM G Cote
Feb 4, 1998·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·S E HsiehJ G Chung
Jun 29, 2005·Environment International·Davide TagliapietraAnnamaria Volpi Ghirardini
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Jul 1, 2010·TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik·K HayashiH Yoshida
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Jun 23, 2006·TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik·K HayashiI Ashikawa
Dec 17, 2019·Plant Disease·Nguyen T M NguyetYoshimichi Fukuta
May 15, 2010·Phytopathology·Mami TakahashiMichiyoshi Arai
Oct 23, 2019·Plant Disease·Yoshimichi FukutaDaigo Makihara
Oct 24, 2008·Phytopathology·Yulin JiaBarbara Valent

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