May 1, 1976

The metabolic activation of the carcinogen 1'-hydroxysafrole in vivo and in vitro and the electrophilic reactivities of possible ultimate carcinogens

Cancer Research
P G WislockiE C Miller

Abstract

Administration of [2',3'-3H]-1'-hydroxysafrole to rats or mice resulted in the formation of hepatic DNA-, ribosomal RNA-, and protein-bound 3H derivatives. Alkaline digestion of the 3H-protein released 0.1 to 0.3% of the 3H as a derivative that was identified as 3'-methylmercaptoisosafrole by its cochromatography in five solvent systems with the synthetic compound. 1'-Hydroxysafrole was metabolized at a low rate by rat and mouse liver cytosols in a 3'-phosphoadenosine 5'-phosphosulfate-dependent reaction to a derivative (presumably the sulfuric acid ester) that was captured by its reaction with RNA. Likewise, 1'-hydroxysafrole was oxidized at a low rate by rat and mouse liver microsomes to 1'-hydroxysafrole-2',3'-oxide in a reduced nicotinamide adenine dinucleotide phosphate-dependent reaction. Both of these electrophilic metabolites are candidate ultimate carcinogenic derivatives of 1'-hydroxysafrole. The electrophilic reactivities of various safrole derivatives with nucleosides were determined to be in the order of 1'-oxosafrole greater than 1'-acetoxysafrole greater than 1'-acetoxysafrole-2',3'-oxide greater than 1'-hydroxysafrole-2',3'-oxide greater than safrole-2',3'-oxide greater than or equal to 1'-oxosafrole-2',3'-oxide...Continue Reading

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Mentioned in this Paper

Tumor Promoters
Guanosine
Sulfurtransferase
Microsomes, Liver
NADP
Nucleosides
15S RNA
Oxidation-Reduction
Dioxoles
Acetyltransferase

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