Dose-response study and threshold estimation of griseofulvin-induced aneuploidy during female mouse meiosis I and II.
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 MII 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.
Marchetti
F
F
Department of Obstetrics and Gynecology, Louisiana State University Medical Center, Shreveport, 71130-3932, USA.
Mailhes
J B
JB
Bairnsfather
L
L
Nandy
I
I
London
S N
SN
D000782:Aneuploidy; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006118:Griseofulvin / Q000494:pharmacology*; D008540:Meiosis / Q000187:drug effects*; D051379:Mice; D008813:Mice, Inbred ICR; D009865:Oocytes / Q000166:cytology / Q000187:drug effects; D011123:Polyploidy; D015053:Zygote / Q000166:cytology / Q000187:drug effects
D000935:Antifungal Agents; D006118:Griseofulvin