Skip to main content
OSTI.GOVU.S. Department of Energy Office of Scientific and Technical Information
U.S. Department of Energy
Office of Scientific and Technical Information
 

Studies on the metabolic activation and deactivation and hepatocarcinogenicity of 1'-hydroxysafrole and 3'-hydroxyisosafrole

Thesis/Dissertation ·
OSTI ID:6514381
1'-Hydroxysafrole is a proximate carcinogenic metabolite of the naturally occurring hepatocarcinogen safrole. The sulfuric acid ester of 1'-hydroxysafrole, 1'-sulfooexysafrole, was shown to be the major ultimate electrophilic and carcinogenic metabolite of 1'-hydroxysafrole in mouse liver. Thus, the covalent binding to hepatic macromolecules and the hepatocarcinogenicity of 1'-hydroxysafrole were 80-90% lower in brachymorphic mice and in mice treated with the sulfotransferase inhibitor pentachlorophenol than in phenotypically normal and previously untreated mice. The sulfuric acid ester of 3'-hydroxyisosafrole was also shown to be electrophilic when chemically synthesized or generated enzymatically in vitro. However, no evidence was obtained for in vivo metabolism of 3'-hydroxyisosafrole to a sulfuric acid ester in the mouse. Administration of 1'-hydroxysafrole to mice in the diet for 4-14 days caused a 90% inhibition of the covalent binding of a subsequent dose of (/sup 3/H)-1'-hydroxysafrole to the hepatic macromolecules. This effect was due to increased detoxification of 1'-hydroxysafrole rather than to an inhibition of metabolic activation. Under the test conditions, 1'-hydroxysafrole had very little, if any, tumor-initiating activity in rat liver, but did exhibit strong promoting activity. This promoting activity was inhibited almost completely by pentachlorophenol, indicating that it was mediated by the electrophilic sulfuric acid ester of 1'-hydroxysafrole.
Research Organization:
Wisconsin Univ., Madison (USA)
OSTI ID:
6514381
Country of Publication:
United States
Language:
English

Similar Records

Hepatic macromolecular covalent binding of the hepatocarcinogen 2,6-dinitrotoluene and its 2,4-isomer in vivo: modulation by the sulfotransferase inhibitors pentachlorophenol and 2,6-dichloro-4-nitrophenol
Journal Article · Sat Sep 01 00:00:00 EDT 1984 · Carcinogenesis (N.Y.); (United States) · OSTI ID:6308113
Predicting the hepatocarcinogenic potential of alkenylbenzene flavoring agents using toxicogenomics and machine learning
Journal Article · Mon Mar 15 00:00:00 EDT 2010 · Toxicology and Applied Pharmacology · OSTI ID:21344888
Hepatocarcinogenesis in the preweanling male B6C3F/sub 1/ mouse with alkenylbenzene derivatives: hepatic DNA adducts, structure-carcinogenicity relationships, and activating mutations in the C-HA-ras proto-oncogene
Thesis/Dissertation · Tue Dec 31 23:00:00 EST 1985 · OSTI ID:6583761

Related Subjects

550201 -- Biochemistry-- Tracer Techniques
560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
BIOLOGICAL EFFECTS
BODY
CARCINOGENESIS
DIGESTIVE SYSTEM
ENZYME INHIBITORS
ENZYMES
ESTERS
GLANDS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LIVER
MAMMALS
METABOLIC ACTIVATION
METABOLITES
MICE
ORGANIC COMPOUNDS
ORGANS
PATHOGENESIS
PHOSPHORUS-GROUP TRANSFERASES
PROMOTERS
RODENTS
SULFURIC ACID ESTERS
TRACER TECHNIQUES
TRANSFERASES
TRITIUM COMPOUNDS
TUMOR PROMOTERS
VERTEBRATES