title: Benomyl induction of brain aromatase and toxic effects in the zebrafish embryo.
abstract: Benomyl is a benzimidazole fungicide that has been widely used on a variety of food crops and ornamental plants. It is known to cause adverse effects on reproductive systems, including decreased testicular and epididymal weights and reduced epididymal sperm counts and fertility. The brain aromatase gene is up-regulated by estrogens and estrogen mimics and considered a target gene to screen estrogen mimics. This study was designed to test the estrogenic potential and toxic effects of benomyl in the zebrafish system, and validated this system as a model that may correspond to the effect of benomyl in rodents. Concentrations of 20 x 10(-6), 40 x 10(-6) and 80 x 10(-6) M of benomyl-treated embryos showed decreased survival, hatching and heart rates, and increased incidence of malformations, such as pericardial edema, spinal lordosis, elongated heart, head edema, eye lens protrusion and caudal fin disappearance. Benomyl induced enhanced green fluorescent protein (EGFP) expression in the mediobasal hypothalamus (MBH) in transient zebrafish embryos with a brain aromatase-based reporter gene. In this study, we determined that benomyl has estrogenic potential based on zebrafish brain aromatase gene induction, and that benomyl is toxic at 20 x 10(-6) M concentration and higher. These results demonstrate the usefulness of zebrafish embryos as an in vivo system to examine the estrogenic and developmental toxic potential of unknown compounds.
authors.affiliation: Department of Laboratory Animal Medicine, College of Veterinary Medicine and BK2 Program for Veterinary Science, Seoul National University, San 56-1, Shinlim-dong, Kwanak-ku, Seoul 151-742, Korea.
authors.forename: Dong-Jae
authors.initials: DJ
authors.lastname: Kim
authors.forename: Seung-Hyeok
authors.initials: SH
authors.lastname: Seok
authors.forename: Min-Won
authors.initials: MW
authors.lastname: Baek
authors.forename: Hui-Young
authors.initials: HY
authors.lastname: Lee
authors.forename: Yi-Rang
authors.initials: YR
authors.lastname: Na
authors.forename: Sung-Hoon
authors.initials: SH
authors.lastname: Park
authors.forename: Hyun-Kyoung
authors.initials: HK
authors.lastname: Lee
authors.forename: Noton Kumar
authors.initials: NK
authors.lastname: Dutta
authors.forename: Koichi
authors.initials: K
authors.lastname: Kawakami
authors.forename: Jae-Hak
authors.initials: JH
authors.lastname: Park
mesh_terms: D000818:Animals; D001141:Aromatase / Q000096:biosynthesis* / Q000235:genetics; D001542:Benomyl / Q000633:toxicity*; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000502:physiology*; D005659:Fungicides, Industrial / Q000633:toxicity*; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D006339:Heart Rate / Q000187:drug effects; D008845:Microinjections; D010957:Plasmids / Q000235:genetics; D016019:Survival Analysis; D013723:Teratogens / Q000633:toxicity; D019895:Transposases / Q000096:biosynthesis / Q000235:genetics; D015027:Zebrafish / Q000502:physiology*
chemical_list: D005659:Fungicides, Industrial; D013723:Teratogens; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D001141:Aromatase; D019895:Transposases; D001542:Benomyl