Dose-response study and threshold estimation of griseofulvin-induced aneuploidy during female mouse meiosis I and II

• Published in: Mutagenesis Vol. 11; no. 2; pp. 195 - 200
• Main Authors: Marchetti, Francesco, Mailhes, John B., Bairnsfather, Lee, Nandy, Indrani, London, Steve N.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.03.1996
• Subjects: Aneuploidy; Animals; Antifungal Agents - pharmacology; Biological and medical sciences; Chemical mutagenesis; Dose-Response Relationship, Drug; Female; Griseofulvin - pharmacology; Medical sciences; Meiosis - drug effects; Mice; Mice, Inbred ICR; Oocytes - cytology; Oocytes - drug effects; Polyploidy; Toxicology; Zygote - cytology; Zygote - drug effects; Chromosomal aberration; Induction; Mutagenicity testing; Toxicity; Rodentia; Pesticides; Aneuploidy; Meiosis; Germinal cell; Oogenesis; Vertebrata; Mammalia; Mouse; Oocyte
• ISSN: 0267-8357; 1464-3804
• DOI: 10.1093/mutage/11.2.195

The relative sensitivity of the two meiotic divisions of mouse oogenesis to griseofulvin (GF)-induced aneuploidy was investigated. The first meiotic division was studied by administering GF 4 h after human chorionic gonadotrophin (HCG) injection and analyzing metaphase II (MII) oocytes, whereas study of the second meiotic division involved treating the females 10 h after HCG and analyzing one-cell (1-Cl) zygotes. Data from previous studies have shown that these treatment times represented the most sensitive times for aneuploidy induction during meioses I and II. The statistical analyses of the data showed that the dose-response curves for aneuploidy induction did not differ quantitatively or qualitatively between the two meiotic divisions. The percentages of hyperploid Mil oocytes and 1-Cl zygotes were significantly higher (P < 0.001) than in the controls for all doses except 125 mg/kg GF. The highest percentages of hyperploid cells were found after administering 1500 mg/kg GF. However, these percentages were not different (P > 0.05) from those observed after 500 or 1000 mg/kg GF, suggesting saturation of the GF aneuploid target(s). These results suggest that the relative sensitivity to GF-induced aneuploidy between the two meiotic divisions of oogenesis are similar. They also suggest the presence of a lower (125 mg/kg) and an upper (500 mg/ kg) threshold for GF-induced aneuploidy.