title: Evaluation of in vivo genotoxicity by thioacetamide in a 28-day repeated-dose liver micronucleus assay using male young adult rats.
abstract: The repeated-dose liver micronucleus (RDLMN) assay has the potential to detect liver carcinogens and can be integrated into general toxicological studies. In this study, thioacetamide (TAA) was tested in 14- and 28-day RDLMN assays to assess the performance of the assay. The test substance, TAA, was administered orally to 6-week-old male Crl:CD (SD) rats once daily for 14 or 28 days at a dosage of 5, 10 or 20mg/kg/day. Hepatocytes were collected approximately 24h after the last TAA administration, and the incidence of micronuclei was assessed. In this study, bone marrow micronucleus assays were also conducted in the same animals. The 14- and 28-day RDLMN assays indicated that none of the TAA dosages significantly increased the proportion of micronucleated hepatocytes. Bone marrow micronucleus assays with TAA also provided negative results. It is known that TAA is a liver carcinogen in mice and rats. In the previous genotoxic studies, the Ames test and the chromosomal aberration test using CHL/IU cells have yielded negative results [1-4]. The liver micronucleus assay using young adult rats singly dosed with TAA (75 and 150mg/kg) also produced negative results [5]. TAA gave positive results only in the mouse bone marrow micronucleus assays [6,7].
authors.affiliation: Hatano Research Institute, Food and Drug Safety Center, 729-5 Ochiai, Hadano-shi, Kanagawa 257-8523, Japan. Electronic address: sui.h@fdsc.or.jp.
authors.forename: Hajime
authors.initials: H
authors.lastname: Sui
authors.affiliation: Hatano Research Institute, Food and Drug Safety Center, 729-5 Ochiai, Hadano-shi, Kanagawa 257-8523, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Matsumoto
authors.affiliation: LSI Medience Corporation, 14-1 Sunayama, Kamisu-shi, Ibaraki 314-0255, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Wako
authors.affiliation: LSI Medience Corporation, 14-1 Sunayama, Kamisu-shi, Ibaraki 314-0255, Japan.
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Kawasako
mesh_terms: D000284:Administration, Oral; D000367:Age Factors; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001853:Bone Marrow / Q000187:drug effects*; D002273:Carcinogens / Q000633:toxicity*; D002869:Chromosome Aberrations / Q000187:drug effects; D003299:Cooperative Behavior; D004334:Drug Administration Schedule; D022781:Hepatocytes / Q000187:drug effects*; D006801:Humans; D007564:Japan; D008099:Liver / Q000187:drug effects*; D008297:Male; D015162:Micronucleus Tests; D051381:Rats; D017207:Rats, Sprague-Dawley; D012156:Reticulocytes / Q000187:drug effects*; D012957:Societies, Pharmaceutical; D013853:Thioacetamide / Q000633:toxicity*
chemical_list: D002273:Carcinogens; D013853:Thioacetamide
keywords: Integrated into general toxicological studies; Repeated-dose liver micronucleus assay; Thioacetamide