Carcinogenicity of 1-hydroxy-3-methylcholanthrene and its electrophilic sulfate ester 1-sulfooxy-3-methylcholanthrene in Sprague-Dawley rats.

Abstract

Previous experiments have demonstrated that the carcinogen 1-hydroxy-3-methylcholanthrene is a metabolite of 3-methylcholanthrene. 1-Sulfooxy-3-methylcholanthrene, prepared by chemical synthesis from 1-hydroxy-3-methylcholanthrene, was shown to be a direct acting electrophilic mutagen and DNA damaging agent. These results imply that 1-hydroxy-3-methylcholanthrene could be metabolically activated to an ultimate electrophilic and carcinogenic form of 1-hydroxy-3-methylcholanthrene and 3-methylcholanthrene in a reaction catalyzed by 3'-phosphoadenosine-5'-phosphosulfate-dependent sulfotransferase activity. 1-Hydroxy-3-methylcholanthrene and its aralkylating reactive ester, 1-sulfooxy-3-methylcholanthrene, were individually administered to groups of 12 female Sprague-Dawley rats at a 0.2 mumol dose, three times weekly, for 20 doses. 1-Sulfooxy-3-methylcholanthrene induced sarcomas at the site of injection in 8 of 12 rats (66%) by 52 weeks, whereas 1-hydroxy-3-methylcholanthrene induced sarcomas at the site of injection in 5 of 12 rats (42%) by 52 weeks. These results, taken together with the results of previous experiments, strongly support the hypothesis that the activated electrophilic mutagen 1-sulfooxy-3-methylcholanthrene plays a major role as an ultimate electrophilic and carcinogenic form of 1-hydroxy-3-methylcholanthrene, a major metabolite of 3-methylcholanthrene.

• Authors: J W Flesher, J Horn, A F Lehner
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 243 Issue 1 Pg. 30-5 (Feb 04 1998) ISSN: 0006-291X [Print] United States
• PMID: 9473474 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Carcinogens
• Mutagens
• Sulfuric Acid Esters
• 1-hydroxy-3-methylcholanthrene
• Methylcholanthrene
• 1-sulfooxy-3-methylcholanthrene

Topics

• Animals
• Carcinogens (chemistry, metabolism, toxicity)
• Electrochemistry
• Female
• Injections, Subcutaneous
• Methylcholanthrene (analogs & derivatives, chemistry, metabolism, toxicity)
• Mutagens (chemistry, metabolism, toxicity)
• Rats
• Rats, Sprague-Dawley
• Sarcoma, Experimental (chemically induced)
• Sulfuric Acid Esters (chemistry, metabolism, toxicity)