The chemotherapeutic agents nocodazole and amsacrine cause meiotic delay and non-disjunction in spermatocytes of mice.
Aneuploidy of germ cells contributes to reduced fertility, foetal wastage and genetic defects. The possible risk of aneuploidy induction by the cancer chemotherapeutic drugs amsacrine (AMSA) and nocodazole (NOC) was investigated in male mice. Two molecular cytogenetic approaches were used: (1) the BrdU-incorporation assay to test the altered duration of meiotic divisions and (2) the sperm-FISH assay to determine aneuploidy induction during meiosis by observing hyperhaploid and diploid sperm. Sperm were sampled from the Caudae epididymes of treated and solvent control males. Single intraperitoneal injections with NOC (35 mg/kg) and AMSA (15 mg/kg) caused a meiotic delay of 24h. The timing of sperm sampling for the sperm-FISH assay was adjusted accordingly, i.e. 23 days after treatment. Mice were treated with 18, 35 and 50 mg/kg of NOC, or 5, 10, 15 and 20 mg/kg of AMSA. Significant dose-dependent increases above the concurrent controls in the frequencies of hyperhaploid sperm were found with both agents. Significant increases in the frequencies of diploid sperm were found only with AMSA. These results provide a basis for genetic counselling of patients under AMSA or NOC chemotherapy. During a period of 3-4 months after the end of chemotherapy, they may stand a higher risk of siring chromosomally abnormal offspring.
Attia
Sabry M
SM
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Nasr City, Cairo, Egypt.
Badary
Osama A
OA
Hamada
Farid M
FM
Hrabé de Angelis
Martin
M
Adler
Ilse-Dore
ID
D000677:Amsacrine / Q000008:administration & dosage / Q000009:adverse effects*; D000782:Aneuploidy; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D017404:In Situ Hybridization, Fluorescence; D007274:Injections, Intraperitoneal; D008297:Male; D008540:Meiosis / Q000187:drug effects* / Q000235:genetics; D051379:Mice; D015739:Nocodazole / Q000008:administration & dosage / Q000009:adverse effects*; D009630:Nondisjunction, Genetic / Q000187:drug effects* / Q000235:genetics; D013090:Spermatocytes / Q000187:drug effects* / Q000378:metabolism
D000970:Antineoplastic Agents; D000677:Amsacrine; D015739:Nocodazole