title: Genotoxicity evaluation of benzene, di(2-ethylhexyl) phthalate, and trisodium ethylenediamine tetraacetic acid monohydrate using a combined rat comet/micronucleus assays.
abstract: As a part of the Japanese Center for the Validation of Alternative Methods (JaCVAM)-initiative international validation study of the in vivo alkaline comet assay (comet assay), we examined DNA damage in the liver, stomach, and bone marrow of rats dosed orally three times with up to 2000 mg/kg of benzene, di(2-ethylhexyl) phthalate, and trisodium ethylenediamine tetraacetic acid monohydrate. All three compounds gave negative results in the liver and stomach. In addition, a bone marrow comet and micronucleus analysis revealed that benzene, but not di(2-ethylhexyl) phthalate or trisodium ethylenediamine tetraacetic acid monohydrate induced a significant increase in the median % tail DNA and micronucleated polychromatic erythrocytes, compared with the respective concurrent vehicle control. These results were in good agreement with the previously reported genotoxicity findings for each compound. The present study has shown that combining the micronucleus test with the comet assay and carrying out these analyses simultaneously is effective in clarifying the mechanism of action of genotoxic compounds such as benzene.
authors.affiliation: Environmental Health Science Laboratory, Sumitomo Chemical Co. Ltd. 3-1-98 Kasugadenaka, Konohana-ku, Osaka 554-8558, Japan. Electronic address: kitamotos3@sc.sumitomo-chem.co.jp.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Kitamoto
authors.affiliation: Environmental Health Science Laboratory, Sumitomo Chemical Co. Ltd. 3-1-98 Kasugadenaka, Konohana-ku, Osaka 554-8558, Japan.
authors.forename: Ryoko
authors.initials: R
authors.lastname: Matsuyama
authors.affiliation: Preclinical Research Laboratories, Dainippon Sumitomo Pharma Co. Ltd. 3-1-98 Kasugadenaka, Konohana-ku, Osaka 554-8558, Japan.
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Uematsu
authors.affiliation: Environmental Health Science Laboratory, Sumitomo Chemical Co. Ltd. 3-1-98 Kasugadenaka, Konohana-ku, Osaka 554-8558, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Ogata
authors.affiliation: Environmental Health Science Laboratory, Sumitomo Chemical Co. Ltd. 3-1-98 Kasugadenaka, Konohana-ku, Osaka 554-8558, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Ota
authors.affiliation: Preclinical Research Laboratories, Dainippon Sumitomo Pharma Co. Ltd. 3-1-98 Kasugadenaka, Konohana-ku, Osaka 554-8558, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Yamada
authors.affiliation: Environmental Health Science Laboratory, Sumitomo Chemical Co. Ltd. 3-1-98 Kasugadenaka, Konohana-ku, Osaka 554-8558, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Miyata
authors.affiliation: Preclinical Research Laboratories, Dainippon Sumitomo Pharma Co. Ltd. 3-1-98 Kasugadenaka, Konohana-ku, Osaka 554-8558, Japan.
authors.forename: Juki
authors.initials: J
authors.lastname: Kimura
authors.affiliation: Preclinical Research Laboratories, Dainippon Sumitomo Pharma Co. Ltd. 3-1-98 Kasugadenaka, Konohana-ku, Osaka 554-8558, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Funabashi
authors.affiliation: Environmental Health Science Laboratory, Sumitomo Chemical Co. Ltd. 3-1-98 Kasugadenaka, Konohana-ku, Osaka 554-8558, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Saito
mesh_terms: D000818:Animals; D001554:Benzene / Q000633:toxicity*; D001853:Bone Marrow / Q000187:drug effects; D020552:Comet Assay / Q000379:methods*; D004249:DNA Damage / Q000187:drug effects*; D053938:DNA Fragmentation / Q000187:drug effects; D004051:Diethylhexyl Phthalate / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004492:Edetic Acid / Q000633:toxicity*; D008099:Liver / Q000187:drug effects; D008297:Male; D015162:Micronucleus Tests / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013270:Stomach / Q000187:drug effects
chemical_list: D004492:Edetic Acid; D004051:Diethylhexyl Phthalate; D001554:Benzene
keywords: Benzene; Di(2-ethylhexyl) phthalate; In vivo comet assay; In vivo rat micronucleus assay; JaCVAM validation study; Trisodium ethylenediamine tetraacetic acid monohydrate