title: A new statistical method for evaluation of L5178Ytk(+/-) mammalian cell mutation data using microwell method.
abstract: A statistical method to evaluate data from the mouse lymphoma L5178Y/tk assay (MLA) using microwell method is proposed. This proposed method is designed for data obtained from a single culture protocol instead of the duplicate culture recommended by United Kingdom Environmental Mutagen Society (UKEMS). The proposed method consists of the following three steps: (1) to apply Dunnett type test for identifying clear negative; (2) to apply a Simpson-Margolin procedure for detecting downturn data; and (3) to apply a trend test to evaluate the dose-dependent increase in mutant frequency (MF). The performance of the proposed method was evaluated through a Monte Carlo study and a case study. False positive rates realized in the Monte Carlo study were comparable with the UKEMS method modified for a single culture protocol with the heterogeneity factors being kept at 1.0. False negative rates were less than those of the modified UKEMS method for dose response patterns with a sharp uprise in higher dose groups, whereas, they were comparable for other patterns. The results of evaluating the data from an International Collaborative Study by the proposed method seem comparable with the UKEMS method. The proposed method enables us to evaluate data from the microwell MLA with a single culture protocol.
authors.affiliation: Pharmaceuticals and Medical Devices Evaluation Center, National Institute of Health Sciences, 3-8-21, Toranomon, Minato-ku, Tokyo 105-8409, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Omori
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Honma
authors.forename: Makoto
authors.initials: M
authors.lastname: Hayashi
authors.forename: Yoriko
authors.initials: Y
authors.lastname: Honda
authors.forename: Isao
authors.initials: I
authors.lastname: Yoshimura
mesh_terms: D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D051379:Mice; D015233:Models, Statistical; D009010:Monte Carlo Method; D009152:Mutagenicity Tests / Q000379:methods*; D009154:Mutation; D015203:Reproducibility of Results; D014407:Tumor Cells, Cultured