title: Studies on the genotoxicity of the mammalian lignans enterolactone and enterodiol and their metabolic precursors at various endpoints in vitro.
abstract: The mammalian lignans enterolactone (ENL) and enterodiol (END) are formed by intestinal bacteria from the plant lignans matairesinol (MAT) and secoisolariciersinol (SEC), respectively, which are ingested with different types of food. ENL and END are weak estrogens. According to epidemiological and biochemical studies, lignans may act as anticarcinogens, but little is known about their genotoxic potential. We have therefore investigated the effects of ENL, END, MAT and SEC on cell-free microtubule assembly and at the following genetic endpoints in cultured male Chinese hamster V79 cells: disruption of the cytoplasmic microtubule complex, induction of mitotic arrest, induction of micronuclei and their characterization by CREST staining, and mutagenicity at the HPRT gene locus. The lignans were tested at concentrations of 200 microM in the cell-free system and 100 microM in cultured cells, which represents the limit of solubility in each assay. The established aneuploidogen diethylstilbestrol and the clastogen 4-nitroquinoline-N-oxide were used as positive reference compounds. As none of the four lignans had any activity at the endpoints studied, we conclude that ENL, END, MAT and SEC are devoid of aneuploidogenic and clastogenic potential under the experimental conditions used in this study.
authors.affiliation: Department of Chemistry, University of Karlsruhe, Germany.
authors.forename: S E
authors.initials: SE
authors.lastname: Kulling
authors.forename: E
authors.initials: E
authors.lastname: Jacobs
authors.forename: E
authors.initials: E
authors.lastname: Pfeiffer
authors.forename: M
authors.initials: M
authors.lastname: Metzler
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity; D000782:Aneuploidy; D000818:Animals; D001419:Bacteria / Q000378:metabolism; D002072:Butylene Glycols / Q000378:metabolism / Q000633:toxicity; D002417:Cattle; D002460:Cell Line; D002474:Cell-Free System; D006224:Cricetinae; D004967:Estrogens / Q000378:metabolism / Q000633:toxicity; D005663:Furans / Q000378:metabolism / Q000633:toxicity; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000382:microbiology; D017705:Lignans / Q000378:metabolism / Q000633:toxicity*; D008297:Male; D015162:Micronucleus Tests; D008870:Microtubules / Q000187:drug effects; D008938:Mitosis / Q000187:drug effects; D009152:Mutagenicity Tests; D009153:Mutagens / Q000378:metabolism / Q000633:toxicity*
chemical_list: D002072:Butylene Glycols; D004967:Estrogens; D005663:Furans; D017705:Lignans; D009153:Mutagens; C068935:matairesinol; C029498:2,3-bis(3'-hydroxybenzyl)butane-1,4-diol; D007041:Hypoxanthine Phosphoribosyltransferase; C060283:secoisolariciresinol; D015107:4-Butyrolactone; C029497:2,3-bis(3'-hydroxybenzyl)butyrolactone