Gap junction intercellular communication mediates the competitive cell proliferation disadvantage of irradiated mouse preimplantation embryos in aggregation chimeras

Vance, M. M. and Wiley, L. M. Gap Junction Intercellular Communication Medi ates the Competitive Cell Proliferation Disadvantage of Irradiated Mouse Pr eimplantation Embryos in Aggregation Chimeras. Radiat. Res. 152, 544-551 (1 999), Gap junction intercellular communication (GJIC) is thought to play a role i n the growth modulation that occurs within cell populations, An example of heterologous growth inhibition (competitive cell proliferation disadvantage ) occurs within mouse aggregation chimeras comprised of irradiated and noni rradiated cleavage-stage embryos, The goal of this investigation was to tes t the hypothesis that GJIC participates in the competitive cell proliferati on disadvantage that is expressed by the irradiated embryo in aggregation c himeras, Specifically, we tested the capacity of the GJIC inhibitor 18 alph a-glycyrrhetinic acid (AGA) to inhibit competitive cell proliferation disad vantage in heterologous aggregation chimeras that were comprised of one emb ryo that was irradiated with 1.0 Gy of Cs-137 gamma rays and then paired wi th one nonirradiated embryo, We found that AGA successfully inhibited fluor escent dye transfer between irradiated and nonirradiated embryos in heterol ogous chimeras. Chronic exposure to AGA prevented competitive cell prolifer ation disadvantage in these radiation chimeras, while exposure to AGA for t he first 15 h of culture (prior to gap junction development) did not preven t competitive cell proliferation disadvantage, An unexpected observation wa s the apparent lack of any effect of inhibiting GJIC by exposure to AGA on blastocyst formation and cell number allocation in the two principal stem c ell lineages of the preimplantation mammalian embryo, trophectoderm and inn er cell mass. (C) 1999 by Radiation Research Society.