Absence of PAPS-dependent bioactivation of 7-hydroxy-methyl-12-methylbenzanthracene (7-OH-DMBA) and N-hydroxy-2-acetylaminofluorene (N-OH-2AAF) in human liver cytosol

Conference · Mon Mar 11 00:00:00 EST 1991 · FASEB Journal (Federation of American Societies for Experimental Biology); (United States)

OSTI ID:5751778

Hirshey, S J; Dowling, T B; Falany, C N ^[1]

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1. Univ. of Rochester, NY (United States)

Cytosolic steroid and phenolic sulfotransferase (ST) activity has been implicated in the metabolic activation of various polycyclic aromatic hydrocarbons to toxic, reactive intermediates, capable of binding to cellular nucleic acids. The formation of these DNA adducts is believed to be the initiation step in the process of chemical carcinogenesis. The 3{prime}-phosphoadenosine 5{prime}-phosphosulfate (PAPS)-dependent activation of two prototypical carcinogens, 7-OH-DMBA and N-OH-2AAF, to reactive metabolites capable of forming DNA adducts has been examined in human and rat liver cytosol. Female Sprague-Dawley rat liver cytosol displays approximately twenty-five fold higher levels of 7-OH-DMBA DNA adduct formation than male rat liver. However, this sex difference is reversed when N-OH-2AAF is used as substrate; male rat liver cytosol possesses approximately sixteen-fold higher levels of DNA adduct formation than female rate liver. In contrast to the bioactivation observed in rat liver cytosol, no PAPS-dependent DNA adduct formation was observed in human liver cytosol with these two carcinogens. The phenol and steroid STs in rat liver cytosol are a heterogeneous group of enzymes, with the levels of many isozymes showing marked differences between the sexes. In comparison, only two forms of phenol and one form of steroid ST, which do not display a sex difference in activity, have been detected in human liver.

• OSTI ID: 5751778
• Report Number(s): CONF-9104107-; CODEN: FAJOE
• Journal Information: FASEB Journal (Federation of American Societies for Experimental Biology); (United States), Vol. 5:4; Conference: 75. annual meeting of the Federation of American Societies for Experimental Biology (FASEB), Atlanta, GA (United States), 21-25 Apr 1991; ISSN 0892-6638
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
BENZANTHRACENE
METABOLIC ACTIVATION
DNA ADDUCTS
BIOSYNTHESIS
FLUORENE
TRANSFERASES
ENZYME ACTIVITY
CARCINOGENESIS
LIVER
MAN
SEX DEPENDENCE
ADDUCTS
ANIMALS
AROMATICS
BODY
CONDENSED AROMATICS
DIGESTIVE SYSTEM
ENZYMES
GLANDS
HYDROCARBONS
MAMMALS
ORGANIC COMPOUNDS
ORGANS
PATHOGENESIS
PRIMATES
PROTEINS
SYNTHESIS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology