title: Structure-Activity Relationships for DNA Damage by Alkenylbenzenes in Turkey Egg Fetal Liver.
abstract: Certain alkenylbenzenes (AB), flavoring chemicals naturally occurring in spices and herbs, are established to be cytotoxic and hepatocarcinogenic in rodents. The purpose of the present study was to determine the DNA damaging potential of key representatives of this class using the Turkey Egg Genotoxicity Assay. Medium white turkey eggs with 22- to 24-day-old fetuses received three injections of nine AB with different carcinogenic potentials: safrole (1, 2 mg/egg), methyl eugenol (2, 4 mg/egg), estragole (20, 40 mg/egg), myristicin (25, 50 mg/egg), elemicin (20, 50 mg/egg), anethole (5, 10 mg/egg), methyl isoeugenol (40, 80 mg/egg), eugenol (1, 2.5 mg/egg), and isoeugenol (1, 4 mg/egg). Three hours after the last injection, fetal livers were harvested for measurement of DNA strand breaks, using the comet assay and DNA adducts formation, using the nucleotide(3) (2)P-postlabeling assay. Estragole, myristicin, and elemicin induced DNA stand breaks. These compounds as well as safrole, methyl eugenol and anethole, at the highest doses tested, induced DNA adduct formation. Methyl isoeugenol, eugenol, and isoeugenol did not induce genotoxicity. The genotoxic AB all had the structural features of either a double bond in the alkenyl side chain at the terminal 2',3'-position, favorable to formation of proximate carcinogenic 1'-hydroxymetabolite or terminal epoxide, or the absence of a free phenolic hydroxyl group crucial for formation of a nontoxic glucuronide conjugate. In contrast, methyl isoeugenol, eugenol and isoeugenol, which were nongenotoxic, possessed chemical features, unfavorable to activation.
authors.affiliation: *Department of Pathology, New York Medical College, Valhalla, New York 10595 and tetyana_kobets@nymc.edu.
authors.forename: Tetyana
authors.initials: T
authors.lastname: Kobets
authors.affiliation: *Department of Pathology, New York Medical College, Valhalla, New York 10595 and.
authors.forename: Jian-Dong
authors.initials: JD
authors.lastname: Duan
authors.affiliation: *Department of Pathology, New York Medical College, Valhalla, New York 10595 and.
authors.forename: Klaus D
authors.initials: KD
authors.lastname: Brunnemann
authors.affiliation: Corporate Compliance Division, Firmenich SA, Rue de la Bergere 7, CH - 1217 Meyrin 2, Switzerland.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Etter
authors.affiliation: Corporate Compliance Division, Firmenich Incorporated, 250 Plainsboro road, Plainsboro, NJ 08536, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Smith
authors.affiliation: *Department of Pathology, New York Medical College, Valhalla, New York 10595 and.
authors.forename: Gary M
authors.initials: GM
authors.lastname: Williams
mesh_terms: D000818:Animals; D001555:Benzene Derivatives / Q000737:chemistry / Q000633:toxicity; D052117:Benzodioxoles / Q000737:chemistry / Q000633:toxicity; D020552:Comet Assay; D018736:DNA Adducts / Q000378:metabolism; D004249:DNA Damage; D047108:Embryonic Development / Q000187:drug effects / Q000235:genetics; D005421:Flavoring Agents / Q000737:chemistry / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D015394:Molecular Structure; D009152:Mutagenicity Tests; D013329:Structure-Activity Relationship; D014422:Turkeys / Q000196:embryology
chemical_list: D001555:Benzene Derivatives; D052117:Benzodioxoles; D018736:DNA Adducts; D005421:Flavoring Agents
keywords: Turkey Egg Genotoxicity Assay (TEGA); alkenylbenzenes (AB); carcinogenicity; chemical structure; genotoxicity