Mechanism of chromosome aberration induction in the mouse egg fertilized with sperm recovered from postmeiotic germ cells treated with methyl methanesulfonate.
Chromosome aberrations induced in spermatozoa to late spermatocytes following treatment with methyl methanesulfonate (MMS) were examined at the first-cleavage metaphase of fertilized eggs in an attempt to clarify the mechanism of chromosomal damage in postmeiotic germ cells. A high frequency of chromosome aberrations was induced in early spermatozoa to mid spermatids, while few chromosome aberrations were observed in early spermatids to late spermatocytes. 3-Aminobenzamide (3AB) potentiated the effect of MMS-induced chromosome aberrations in spermatozoa to mid spermatids indicating that a large amount of DNA lesions produced at these stages during spermatogenesis were not repaired prior to fertilization of the oocytes. Furthermore, from the cell-cycle analysis of the repair capacity in the fertilized egg it became clear that the lesions which remained in sperm until fertilization could be divided into 2 types: (1) DNA-strand breaks induced by stress in the chromatin structure produced by protamine alkylation; these lesions were converted to chromosome-type aberrations by 3AB treatment of the eggs during G1 phase; and (2) alkylated DNA which produces apurinic or apyrimidinic sites, of which there were a significant number mainly converted to chromatid exchanges by 3AB treatment of the eggs during S phase. This type of lesion appears to be constantly induced through all spermiogenic stages in contrast to the former type of lesion which is induced specifically during the stage of protamine maturation.
Matsuda
Y
Y
Division of Genetics, National Institute of Radiological Sciences, Chiba, Japan.
Tobari
I
I
Maemori
M
M
Seki
N
N
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology; D002869:Chromosome Aberrations; D003561:Cytarabine / Q000494:pharmacology; D005260:Female; D006918:Hydroxyurea / Q000494:pharmacology; D008297:Male; D008540:Meiosis; D008741:Methyl Methanesulfonate / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D009153:Mutagens / Q000494:pharmacology; D010063:Ovum / Q000166:cytology / Q000187:drug effects*; D012854:Sister Chromatid Exchange; D013094:Spermatozoa / Q000166:cytology / Q000187:drug effects*; D015053:Zygote / Q000166:cytology* / Q000187:drug effects
D001549:Benzamides; D009153:Mutagens; D003561:Cytarabine; D002110:Caffeine; C025160:3-aminobenzamide; D008741:Methyl Methanesulfonate; D006918:Hydroxyurea