TRANSMITTED PROLIFERATION DISADVANTAGE FROM MOUSE OOCYTES LABELED IN-VIVO WITH [H-3] THYMIDINE - RADIOSENSITIVE TARGET CONSIDERATIONS

This study was conducted to test the hypothesis that a nuclear target is involved in the embryonic cell proliferation disadvantage transmitt ed by irradiated mouse oocytes and detected by the chimera assay. In t his assay, the cells from the irradiated embryo exhibit a competitive cell proliferation disadvantage when they are challenged by direct cel l-cell contact with cells from a normal embryo in an aggregation chime ra. Here, six pregnant CD-1 mice received a total of 1.85 TBq tritiate d thymidine (TdR) delivered by multiple intraperitoneal injections dur ing days 13-15 postconception. Six more pregnant mice were sham-inject ed to provide control embryos. Sixty randomly selected female progeny were mated at 47 days of age and their 4-cell embryos tested in the ch imera assay. The mean proliferation ratio (PR, number of cells from th e experimental embryo divided by total cell number of the chimera) for experimental chimeras was 0.45+/-0.02 SE (n=43), which was significan tly less than the mean PR of 0.49+/-0.01 SE (n=47; p=0.02) for control chimeras. This entire experiment was repeated, with similar results. A comparison for TdR confined to the nucleus (i.e., mean beta-ray rang e is only 0.7 mu m) with the relationship for uniform irradiation by C s-137 gamma-rays demonstrates that these two very different modes of d ose delivery produce essentially identical PRs. These results in vivo suggest a nuclear DNA target for embryonic cell proliferation disadvan tage consistent with our previous findings in vitro.