Structure-activity studies of the carcinogenicities in the mouse and rat of some naturally occurring and synthetic alkenylbenzene derivatives related to safrole and estragole
- PMID: 6825084
Structure-activity studies of the carcinogenicities in the mouse and rat of some naturally occurring and synthetic alkenylbenzene derivatives related to safrole and estragole
Abstract
Twenty-three naturally occurring and synthetic alkenylbenzene derivatives structurally related to the hepatocarcinogen safrole (1-allyl-3,4-methylenedioxybenzene) were assayed for their hepatocarcinogenicity in mice. Some of these compounds (safrole, estragole, eugenol, anethole, methyleugenol, myristicin, elemicin, and dill and parsley apiols) may be ingested in very small amounts by human as natural components of certain spices, essential oils, or vegetables. Estragole (1-allyl-4-methoxybenzene) and its proximate carcinogenic metabolite 1'-hydroxyestragole, previously shown to induce hepatic tumors when administered to male CD-1 mice only during the preweaning period, also induced hepatic tumors on administration for 12 months in the diet of female CD-1 mice. Eugenol (1-allyl-4-hydroxy-3-methoxybenzene) and anethole (trans-4-methoxy-1-propenylbenzene) were inactive in this assay; they were also inactive when administered i.p. during the preweaning period at total doses of up to 9.45 mumol/mouse to male CD-1 or C57BL/6 x C3H F1 (hereafter called B6C3F1) mice. Methyleugenol (1-ally-3,4-dimethoxybenzene) and its 1'-hydroxy metabolite had activities similar to those of estragole and its 1'-hydroxy metabolite for the induction of hepatic tumors in male B6C3F1 mice treated prior to weaning; 1-allyl-1'-hydroxy-4-methoxynaphthalene was somewhat less active. At the levels tested, myristicin (1-allyl-5-methoxy-3,4-methylenedioxybenzene), elemicin (1-allyl-3,4,5-trimethoxybenzene) and its 1'-hydroxy metabolite, dill apiol (1-allyl-2,3-dimethoxy-4,5-methylenedioxybenzene), parsley apiol (1-allyl-2,5-dimethoxy-3,4-methylenedioxybenzene), 1'-hydroxyallybenzene, 3'-hydroxyanethole, and benzyl and anisyl alcohols had no detectable activity for the initiation of hepatic tumors on administration to male mice prior to weaning. The acetylenic derivative 1'-hydroxy-2',3'-dehydroestragole was much more active than either 1'-hydroxysafrole or 1'-hydroxyestragole when administered to preweanling mice. The 2',3'-oxides of safrole, estragole, eugenol, and 1'-hydroxysafrole, which are metabolites of these alkenylbenzenes, had little or no activity in this test. The 2',3'-oxides of safrole and estragole and their 1'-hydroxy derivatives likewise had little or no activity for the induction of lung adenomas in female A/J mice or for the induction of tumors on repetitive injections s.c. in male Fischer rats. However, the 2',3'-oxides of safrole, estragole, eugenol, 1'-hydroxysafrole, and 1'-hydroxyestragole, when administered topically to female CD-1 mice at relatively high doses, initiated benign skin tumors that could be promoted with croton oil.
Similar articles
-
Structure-activity studies of the hepatocarcinogenicities of alkenylbenzene derivatives related to estragole and safrole on administration to preweanling male C57BL/6J x C3H/HeJ F1 mice.Cancer Res. 1987 May 1;47(9):2275-83. Cancer Res. 1987. PMID: 3567921
-
Major role of hepatic sulfotransferase activity in the metabolic activation, DNA adduct formation, and carcinogenicity of 1'-hydroxy-2',3'-dehydroestragole in infant male C57BL/6J x C3H/HeJ F1 mice.Cancer Res. 1985 Nov;45(11 Pt 1):5310-20. Cancer Res. 1985. PMID: 3863702
-
Strong evidence from studies with brachymorphic mice and pentachlorophenol that 1'-sulfoöxysafrole is the major ultimate electrophilic and carcinogenic metabolite of 1'-hydroxysafrole in mouse liver.Cancer Res. 1983 Nov;43(11):5163-73. Cancer Res. 1983. PMID: 6577945
-
Flavonoids and alkenylbenzenes: mechanisms of mutagenic action and carcinogenic risk.Mutat Res. 2005 Jul 1;574(1-2):124-38. doi: 10.1016/j.mrfmmm.2005.01.028. Epub 2005 Mar 31. Mutat Res. 2005. PMID: 15914212 Review.
-
The metabolic activation and nucleic acid adducts of naturally-occurring carcinogens: recent results with ethyl carbamate and the spice flavors safrole and estragole.Br J Cancer. 1983 Jul;48(1):1-15. doi: 10.1038/bjc.1983.151. Br J Cancer. 1983. PMID: 6191767 Free PMC article. Review.
Cited by
-
The Mediterranean Species Calendula officinalis and Foeniculum vulgare as Valuable Source of Bioactive Compounds.Molecules. 2024 Jul 30;29(15):3594. doi: 10.3390/molecules29153594. Molecules. 2024. PMID: 39124999 Free PMC article. Review.
-
Formation of DNA Adducts by 1-Methoxy-3-indolylmethylalcohol, a Breakdown Product of a Glucosinolate, in the Mouse: Impact of the SULT1A1 Status-Wild-Type, Knockout or Humanised.Int J Mol Sci. 2024 Mar 29;25(7):3824. doi: 10.3390/ijms25073824. Int J Mol Sci. 2024. PMID: 38612635 Free PMC article.
-
Characterization and Investigation of Novel Benzodioxol Derivatives as Antidiabetic Agents: An In Vitro and In Vivo Study in an Animal Model.Biomolecules. 2023 Oct 6;13(10):1486. doi: 10.3390/biom13101486. Biomolecules. 2023. PMID: 37892167 Free PMC article.
-
Urinary Excretion of Mercapturic Acids of the Rodent Carcinogen Methyleugenol after a Single Meal of Basil Pesto: A Controlled Exposure Study in Humans.Chem Res Toxicol. 2023 Nov 20;36(11):1753-1767. doi: 10.1021/acs.chemrestox.3c00212. Epub 2023 Oct 24. Chem Res Toxicol. 2023. PMID: 37875262 Free PMC article.
-
Refine and Strengthen SAR-Based Read-Across by Considering Bioactivation and Modes of Action.Chem Res Toxicol. 2023 Sep 18;36(9):1532-1548. doi: 10.1021/acs.chemrestox.3c00156. Epub 2023 Aug 18. Chem Res Toxicol. 2023. PMID: 37594911 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Other Literature Sources
Medical