Induction of chromosomal aberrations in mouse zygotes by acrylamide treatment of male germ cells and their correlation with dominant lethality and heritable translocations.
The objectives of this research were: 1) to investigate the time course of the cytogenetic defects induced by acrylamide (AA) treatment (5 x 50 mg/kg) of male germ cells in first-cleavage zygote metaphases using PAINT/DAPI analysis, and 2) to characterize the correlation between chromosomal aberrations at first cleavage, dominant lethality, and heritable translocations. PAINT/DAPI analysis employs multicolor fluorescence in situ hybridization painting plus DAPI staining to detect both stable and unstable chromosomal aberrations at first-cleavage metaphase of the zygote. High levels of chromosomally defective zygotes were detected after mating at all postmeiotic stages (20-190-fold, P < 0.001). Early spermatozoa (6.5 d post-treatment) were the most sensitive, with 76% of the zygotes carrying cytogenetic defects. A significant 10-fold increase was also detected 27.5 d post-treatment, indicating that AA had a cytogenetic effect on meiotic stages. PAINT/DAPI analysis revealed that: 1) AA-induced chromosomal breaks occurred at random, and 2) the frequencies of symmetrical and asymmetrical exchanges were similar at all mating days, except 9.5 d after AA treatment, where significantly (P < 0.02) more asymmetrical aberrations were found. Furthermore, the proportions of zygotes carrying unstable and stable chromosomal aberrations followed a similar post-treatment time course as the proportions of dominant lethality among embryos and heritable translocations among offspring. These findings indicate that PAINT/DAPI analysis of zygotic metaphases is a promising method for detecting male germ cell mutagens capable of inducing chromosomal aberrations and for evaluating the associated risks for embryonic loss and balanced translocations at birth.
Marchetti
F
F
Biology and Biotechnology Research Program, Lawrence Livermore National Laboratory, Livermore, California 94550, USA. marchetti2@poptart.llnl.gov
Lowe
X
X
Bishop
J
J
Wyrobek
A J
AJ
D020106:Acrylamide; D000178:Acrylamides / Q000633:toxicity*; D000818:Animals; D002869:Chromosome Aberrations; D004249:DNA Damage; D005260:Female; D005306:Fertilization; D008297:Male; D051379:Mice; D013091:Spermatogenesis / Q000187:drug effects* / Q000235:genetics; D013094:Spermatozoa / Q000187:drug effects*; D014178:Translocation, Genetic; D015053:Zygote
D000178:Acrylamides; D020106:Acrylamide