Ž . Mutation Research 441 1999 181–190 www.elsevier.comrlocatergentox Community address: www.elsevier.comrlocatermutres Griseofulvin-induced aneuploidy and meiotic delay in male mouse germ cells: detected by using conventional cytogenetics and three-color FISH Shi Qinghua a,b , T.E. Schmid a , I.-D. Adler a, ) a Institut fuer Saeugetiergenetik, GSF Forschungszentrum fuer Umwelt und Gesundheit, Ingolstaedter Landstr. 1, 85764 Neuherberg, Germany b Department of Biology, Nanjing Normal UniÕersity, Nanjing 210097, China Received 30 September 1998; received in revised form 2 March 1999; accepted 3 March 1999 Abstract Ž . Griseofulvin GF was tested in male mouse germ cells for the induction of meiotic delay and aneuploidy. Starved mice were orally treated with 500, 1000 and 2000 mgrkg of GF in corn oil and testes were sampled 22 h later for meiotic delay Ž . analysis and chromosome counting in spermatocytes at the second meiotic metaphase MMII . A dose-related increase in Ž . meiotic delay by dose-dependently arresting spermatocytes in first meiotic metaphase MMI orrand prolonging interkinesis was observed. Hyperhaploid MMII cells were not significantly increased. Sperm were sampled from the Caudae epididymes Ž . 22 days after GF-treatment of the males for three-color fluorescence in situ hybridization FISH . The frequencies of diploidies were 0.01–0.02% in sperm of the solvent control animals and increased dose-dependently to 0.03%, 0.068% and 0.091%, respectively, for 500, 1000 and 2000 mgrkg of GF. The frequencies of disomic sperm were increased significantly above the controls in all GF-treated groups but showed no dose response. The data for individual classes of disomic sperm indicated that MII was more sensitive than MI to GF-induced non-disjunction in male mice. A comparison of the present data from male mice and literature data from female mice suggests that mouse oocytes are more sensitive than mouse spermatocytes to GF-induced meiotic delay and aneuploidy. q 1999 Elsevier Science B.V. All rights reserved. Ž . Keywords: Griseofulvin; Meiotic delay; Fluorescence in situ hybridization FISH ; Aneuploidy; Sperm; Mouse 1. Introduction Aneuploidy is the most common class of chromo- some abnormalities in humans, occurring in at least 0.3% of liveborn children, approximately 4% of wx stillbirths and 35% of spontaneous abortions 1 . It is also the most commonly known cause of mental and ) Corresponding author. Tel.: q49-89-3187-2302; Fax: q49- 89-3187-2210; E-mail: adler@gsf.de physical retardation in newborns. Despite the high frequency of aneuploidy and its great burden on human health, the etiology and mechanisms of these genetic disorders are still poorly understood. Even less information is available about the role that ex- ogenous agents such as chemical and physical fac- wx tors have on the genesis of human aneuploidy 1. Different experimental approaches have been devel- oped and applied to investigate aneuploidy induction w x in male germ cells of rodents 2–4 . For classical 1383-5718r99r$ - see front matter q 1999 Elsevier Science B.V. All rights reserved. Ž . PII: S1383-5718 99 00046-7