title: SFTG international collaborative study on in vitro micronucleus test V. Using L5178Y cells.
abstract: In this report, results are presented from an international study of the in vitro micronucleus assay using mouse lymphoma L5178Y cells. This study was coordinated by an organizing committee supported by the SFTG (the French branch of the European Environmental Mutagen Society). Test chemicals included mannitol, bleomycin, 5-fluorouracil, colchicine and griseofulvin. Mitomycin C was used as a positive control. Each chemical was evaluated in at least two laboratories following a variety of different protocols (short and long exposures, varying recovery times, with and without cytochalasin B) in order to help determine a standard protocol for routine testing in mouse lymphoma L5178Y cells. Mannitol was the only exception, being tested in only one laboratory. Mannitol was negative, while bleomycin induced a concentration-dependent increase in micronucleated cells. Equivocal results were obtained for 5-fluorouracil, colchicine and griseofulvin. High levels of cytotoxicity interfered with the assessment of aneuploidy for colchicine and griseofulvin, preventing the ability to obtain clear results in all the treatment schedules. Experiments with 5-fluorouracil, colchicine and griseofulvin showed that both short and long treatment times are required as each compound was detected using one or more treatment protocol. No clear differences were seen in the sensitivity or accuracy of the responses in the presence of absence of cytochalasin B. It was also found that a recovery period may help to detect compounds which induce a genotoxicity associated to a reduction in cell number or cell proliferation. Overall, the results of the present study show that mouse lymphoma L5178Y cells are suitable for the in vitro micronucleus assay.
authors.affiliation: GlaxoSmithKline Research & Development, Ware, Herts, England.
authors.forename: Jo
authors.initials: J
authors.lastname: Oliver
authors.forename: Jean-Roch
authors.initials: JR
authors.lastname: Meunier
authors.forename: Takumi
authors.initials: T
authors.lastname: Awogi
authors.forename: Azeddine
authors.initials: A
authors.lastname: Elhajouji
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Ouldelhkim
authors.forename: Nicole
authors.initials: N
authors.lastname: Bichet
authors.forename: Veronique
authors.initials: V
authors.lastname: Thybaud
authors.forename: Giocondo
authors.initials: G
authors.lastname: Lorenzon
authors.forename: Daniel
authors.initials: D
authors.lastname: Marzin
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Lorge
mesh_terms: D024422:Aneugens / Q000633:toxicity; D000818:Animals; D001761:Bleomycin / Q000633:toxicity; D003078:Colchicine / Q000633:toxicity; D005472:Fluorouracil / Q000633:toxicity; D006118:Griseofulvin / Q000633:toxicity; D066298:In Vitro Techniques; D007391:International Cooperation; D007940:Leukemia L5178; D008353:Mannitol / Q000633:toxicity; D051379:Mice; D015162:Micronucleus Tests / Q000379:methods*; D009153:Mutagens / Q000633:toxicity*
chemical_list: D024422:Aneugens; D009153:Mutagens; D001761:Bleomycin; D006118:Griseofulvin; D008353:Mannitol; D003078:Colchicine; D005472:Fluorouracil