Griseofulvin-induced aneuploidy and meiotic delay in male mouse germ cells: detected by using conventional cytogenetics and three-color FISH.
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 mg/kg of GF in corn oil and testes were sampled 22 h later for meiotic delay analysis and chromosome counting in spermatocytes at the second meiotic metaphase (MMII). A dose-related increase in meiotic delay by dose-dependently arresting spermatocytes in first meiotic metaphase (MMI) or/and prolonging interkinesis was observed. Hyperhaploid MMII cells were not significantly increased. Sperm were sampled from the Caudae epididymes 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 mg/kg 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.
Shi
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Institut fuer Saeugetiergenetik, GSF Forschungszentrum fuer Umwelt und Gesundheit, Ingolstaedter Landstr. 1, 85764 Neuherberg, Germany.
Schmid
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Adler
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D000782:Aneuploidy; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D002869:Chromosome Aberrations; D015342:DNA Probes / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004822:Epididymis / Q000187:drug effects; D005260:Female; D006118:Griseofulvin / Q000494:pharmacology*; D007091:Image Processing, Computer-Assisted; D017404:In Situ Hybridization, Fluorescence / Q000662:veterinary; D008297:Male; D008540:Meiosis / Q000187:drug effects*; D051379:Mice; D008856:Microscopy, Fluorescence / Q000662:veterinary; D011897:Random Allocation; D013094:Spermatozoa / Q000187:drug effects*
D000935:Antifungal Agents; D015342:DNA Probes; D006118:Griseofulvin