title: JaCVAM-organized international validation study of the in vivo rodent alkaline comet assay for the detection of genotoxic carcinogens: I. Summary of pre-validation study results.
abstract: The in vivo rodent alkaline comet assay (comet assay) is used internationally to investigate the in vivo genotoxic potential of test chemicals. This assay, however, has not previously been formally validated. The Japanese Center for the Validation of Alternative Methods (JaCVAM), with the cooperation of the U.S. NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM)/the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), the European Centre for the Validation of Alternative Methods (ECVAM), and the Japanese Environmental Mutagen Society/Mammalian Mutagenesis Study Group (JEMS/MMS), organized an international validation study to evaluate the reliability and relevance of the assay for identifying genotoxic carcinogens, using liver and stomach as target organs. The ultimate goal of this validation effort was to establish an Organisation for Economic Co-operation and Development (OECD) test guideline. The purpose of the pre-validation studies (i.e., Phase 1 through 3), conducted in four or five laboratories with extensive comet assay experience, was to optimize the protocol to be used during the definitive validation study.
authors.affiliation: Mitsubishi Tanabe Pharma Co., Chiba, Japan. Electronic address: Uno.Yoshifumi@ma.mt-pharma.co.jp.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Uno
authors.affiliation: National Institute of Health Sciences, Tokyo, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Kojima
authors.affiliation: Kobe University Hospital (formerly Doshisha University, Kyoto), Kobe, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Omori
authors.affiliation: Joint Research Centre of the European Commission, Ispra, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Corvi
authors.affiliation: National Institute of Health Sciences, Tokyo, Japan.
authors.forename: Masamistu
authors.initials: M
authors.lastname: Honma
authors.affiliation: Innovative Toxicology Consulting, LLC, FL, USA.
authors.forename: Leonard M
authors.initials: LM
authors.lastname: Schechtman
authors.affiliation: National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
authors.forename: Raymond R
authors.initials: RR
authors.lastname: Tice
authors.affiliation: Huntingdon Life Sciences, Cambs, UK.
authors.forename: Brian
authors.initials: B
authors.lastname: Burlinson
authors.affiliation: Boehringer Ingelheim Pharmaceuticals Inc., CT, USA.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Escobar
authors.affiliation: Merck Research Laboratories, PA, USA.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Kraynak
authors.affiliation: Hatano Research Institute, Food Drug Safety Center, Kanagawa, Japan.
authors.forename: Yuzuki
authors.initials: Y
authors.lastname: Nakagawa
authors.affiliation: University of Shizuoka, Shizuoka, Japan.
authors.forename: Madoka
authors.initials: M
authors.lastname: Nakajima
authors.affiliation: BioReliance, MD, USA.
authors.forename: Kamala
authors.initials: K
authors.lastname: Pant
authors.affiliation: Kinki University, Osaka, Japan.
authors.forename: Norihide
authors.initials: N
authors.lastname: Asano
authors.affiliation: St. George's, University of London, London, UK.
authors.forename: David
authors.initials: D
authors.lastname: Lovell
authors.affiliation: National Institute of Health Sciences, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Morita
authors.affiliation: National Institute of Health Sciences, Tokyo, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ohno
authors.affiliation: Biosafety Research Center, Foods, Drugs and Pesticides, Shizuoka, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Hayashi
mesh_terms: D000818:Animals; D002273:Carcinogens / Q000032:analysis*; D020552:Comet Assay / Q000379:methods* / Q000592:standards*; D004249:DNA Damage; D005060:Europe; D017408:Guidelines as Topic; D008099:Liver / Q000187:drug effects; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012958:Societies, Scientific; D013270:Stomach / Q000187:drug effects; D014481:United States
chemical_list: D002273:Carcinogens
keywords: Comet assay; Genotoxicity; In vivo; JaCVAM; Rodent; Validation study