title: Evaluation of methyl methanesulfonate, 2,6-diaminotoluene and 5-fluorouracil: Part of the Japanese center for the validation of alternative methods (JaCVAM) international validation study of the in vivo rat alkaline comet assay.
abstract: As a part of the Japanese Center for the Validation of Alternative Methods (JaCVAM)-initiative international validation study of the in vivo rat alkaline comet assay (comet assay), we examined methyl methanesulfonate, 2,6-diaminotoluene, and 5-fluorouracil under coded test conditions. Rats were treated orally with the maximum tolerated dose (MTD) and two additional descending doses of the respective compounds. In the MMS treated groups liver and stomach showed significantly elevated DNA damage at each dose level and a significant dose-response relationship. 2,6-diaminotoluene induced significantly elevated DNA damage in the liver at each dose and a statistically significant dose-response relationship whereas no DNA damage was obtained in the stomach. 5-fluorouracil did not induce DNA damage in either liver or stomach.
authors.affiliation: Novartis Institutes for BioMedical Research, Novartis Pharma AG, Switzerland. Electronic address: ulla.plappert_helbig@novartis.com.
authors.forename: Ulla
authors.initials: U
authors.lastname: Plappert-Helbig
authors.affiliation: Novartis Institutes for BioMedical Research, Novartis Pharma AG, Switzerland.
authors.forename: Ursula
authors.initials: U
authors.lastname: Junker-Walker
authors.affiliation: Novartis Institutes for BioMedical Research, Novartis Pharma AG, Switzerland.
authors.forename: Hans-Joerg
authors.initials: HJ
authors.lastname: Martus
mesh_terms: D000818:Animals; D020552:Comet Assay / Q000379:methods*; D004249:DNA Damage / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005472:Fluorouracil / Q000633:toxicity*; D008099:Liver / Q000187:drug effects; D008297:Male; D008741:Methyl Methanesulfonate / Q000633:toxicity*; D010655:Phenylenediamines / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D013270:Stomach / Q000187:drug effects
chemical_list: D010655:Phenylenediamines; D008741:Methyl Methanesulfonate; C025235:2,6-diaminotoluene; D005472:Fluorouracil
keywords: 2,6-Diaminotoluene; 5-Fluorouracil; In vivo mammalian alkaline comet assay; In vivo rat comet assay; JaCVAM validation study; Methyl methanesulfonate