RELATIONSHIP BETWEEN CHROMOSOME ABERRATIONS IN THE FIRST-CLEAVAGE METAPHASES AND UNSCHEDULED DNA SYNTHESIS FOLLOWING PATERNAL MMS TREATMENT

Abstract

To gain further insight into the mechanisms of induction of dominant lethal mutations, the relationship between the chromosome aberrations in male pronuclei and unscheduled DNA synthesis (UDS) in spermatogenesis during 42 days after treatment with MMS was examined. Nine-week-old hybrid mice (C57BL/6J×DBA/2) were used in all experiments. For the detection of chromosome aberrations in first-cleavage metaphases, chromosome preparations were made by a new technique. UDS in male germ cells was detected by Sega's procedures (Sega et al. 1974).
The frequency of eggs with one or more chromosome aberrations at the first-cleavage metaphase showed a close correlation with the high frequency of dominant lethals during 1 to 14 days after treatment. In particular, eggs recovered during 7 to 10 days were found to have more than 8 chromosome aberrations per egg. The types of structural aberrations observed were predominantly chromosome-types including fragments and dicentrics. The development of 3-day eggs obtained from females mated 7-10 days after treatment of the male mice with MMS was markedly delayed, with degenerated blastomeres and micronuclei. However, unfertilized eggs were not observed in this period. These results show that even sperm with MMS-induced lesions is capable of fertilization. On the other hand, UDS was detected during 16 to 24 days after treatment, with a peak at 20 days. Consequently, an opposite correlation was observed between UDS and dominant lethals induced by MMS in spermatogenic stages.
These results suggest that chromosome damage induced from late spermatids to spermatozoa, where UDS was not observed, may produce chromosome aberrations in male pronuclei; these fertilized eggs with chromosome aberrations would show dominant lethal mutations resulting from early cleavage death.