Hepatocarcinogenicity of estragole (1-allyl-4-methoxybenzene) and 1'-hydroxyestragole in the mouse and mutagenicity of 1'-acetoxyestragole in bacteria.

Abstract

Approximately 20% of a dose of estragole, a naturally occurring flavoring agent, was excreted in the urine of outbred male CD -1 mice as a conjuage (presumably the glucuronide) of 1'-hydroxyestragole, Estragole and its 1'-hydroxy metabolite caused significant increases in the incidences of hepatocellular carcinomas in male CD-1 mice that received the compounds by sc injection at 1-22 days of age. Estragole induced hepatocellular carcinomas by 15 months in 23 and 39% of the mice that received total doses of 4.4 and 5.2 mumoles, respectively, and lived to an age of 12 months or more. Of the 12-month survivors given a total dose of 4.4 mumoles of 1'-hydroxyestragole, 70% developed hepatocellular carcinomas; the incidence in mice that received only the vehicle (trioctanoin) was 12%. Multiple tumors ocurred in 5, 28, 64, and 0%, respectively, of the mice in each of these 4 groups. Of the mice given a total dose of 4.4 mumoles of 1'-hydroxysafrole, 59developed hepatocellular carcinomas; 39% of the mice bore multiple liver tumors. As previsously demonstrated for 1'-acetoxysafrole, 1'-acetoxyestragole and 1'-acetoxy-1-allyl-4-methoxynaphthalene reacted nonenzymatically with guanosine and inosine to form adducts. These electrophilic esters were strongly mutagenic for the Salmonella typhimurium missense mutant TA100. 1'-Acetoxyallybenzene had little or no activity in either of these tests. Attempts to demonstrate liver-mediated mutagenicty for 1'-hydroxysafrole and 1'-hydroxyestragole in the bacterial test system were unsuccessful.

• Authors: N R Drinkwater, E C Miller, J A Miller, H C Pitot
• Journal: Journal of the National Cancer Institute (J Natl Cancer Inst) Vol. 57 Issue 6 Pg. 1323-31 (Dec 1976) ISSN: 0027-8874 [Print] United States
• PMID: 187802 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Allylbenzene Derivatives
• Anisoles
• Carcinogens
• Flavoring Agents
• Glucuronates
• Mutagens
• Nucleosides
• 1'-hydroxyestragole
• estragole

Topics

• Allylbenzene Derivatives
• Animals
• Animals, Newborn
• Anisoles (metabolism, toxicity)
• Carcinogens
• Carcinoma, Hepatocellular (chemically induced, pathology)
• Flavoring Agents (metabolism, toxicity)
• Glucuronates (metabolism)
• Liver (metabolism)
• Liver Neoplasms (chemically induced, pathology)
• Male
• Mice
• Mutagens
• Neoplasms, Experimental (chemically induced, pathology)
• Nucleosides (metabolism)
• Salmonella typhimurium (drug effects)