Electrophilic Sulfuric Acid Ester Metabolites of Hydroxy-Methyl Aromatic Hydrocarbons as Precursors of Hepatic Benzylic DNA Adducts in Vivo

  • James A. Miller
  • Young-Jooh Surh
  • Amy Liem
  • Elizabeth C. Miller
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 283)


In recent years work in our laboratory has identified the principal ultimate electrophilic and carcinogenic metabolites formed in vivo in mouse liver from several classes of chemical carcinogens, especially in relation to DNA adduct and hepatoma formation. These carcinogens comprised several naturally occuring alkenylbenzenes and their proximate carcinogenic l’-hydroxy metabolites (Boberg et al., 1983; Wiseman et al., 1987), the synthetic alkyne, l’-hydroxy-2’,3-’dehydroestragole (Fennell et al., 1985); 4-aminoazobenzene and its proximate carcinogenic metabolite, N-hydroxy-4aminoazobenzene (Delclos et al., 1986), and 2-acetylamino-fluorene (Lai et al., 1985, 1987, 1988). In each of these cases, the ultimate reactive carcinogen leading to DNA adduct formation and hepatoma formation appears to be an electrophilic sulfuric acid ester generated by one or more 3’-phospho-adenosine-5’-phosphosulfate (PAPS)-dependent sulfotransferase activities in the liver cytosol. It appears possible from the work of others that the carcinogenic activity of 2,6-dinitrotoluene (Kedderis et al., 1984; Chism and Rickert, 1989), certain nitrosamine derivatives (Sterzel and Eisenbrand, 1986; Kokkinakis et al., 1986; Kroeger-Koepke et al., 1989), and certain drugs with 13-aminoalcohol moiety such as pronethalol (Bicker and Fischer, 1974) may also involve sulfuric acid ester metabolites. The oncogenic purine derivative, 3-hydroxyxanthine has also been thought to be activated by sulfotransferase activity (Stöhrer et al., 1972; Anderson et al., 1978).


Polycyclic Aromatic Hydrocarbon Liver Cytosol Testosterone Propionate Estradiol Benzoate Carcinogenic Metabolite 
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Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • James A. Miller
    • 1
  • Young-Jooh Surh
    • 1
  • Amy Liem
    • 1
  • Elizabeth C. Miller
    • 1
  1. 1.McArdle Laboratory for Cancer Research and Environmental Toxicology CenterUniversity of Wisconsin Medical SchoolMadisonUSA

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