Cell-cycle alterations underlie XXXX -induced teratogenesis in the @entity1573 embryo.

@entity137 @entity308 @entity5611 @entity786 @entity600 @entity1573 @entity204
BACKGROUND: @entity786 (CP) embryotoxicity was documented in several studies on different experimental models. We investigate quantitatively the relationship between the embryotoxic effect of CP and the disturbance of the cell-cycle using flow cytometry. METHODS: @entity1573 embryos on Days 2-4 were treated with 0.5, 1, 2, 4, 8, and 16 microg doses of pure substance of CP by intraamniotic or subgerminal administration routes. Cell-cycle analysis was carried out in the brain, limb buds, hearts, and facial outgrowths dissected from the embryos 6 hr after administration. Samples of nuclear suspensions were obtained by enzymatic and mechanical disintegration of solid tissues in collagenase-dispase, followed by detergent and RNA-ase mediated cytolysis. Nuclei were stained by @entity5611 . RESULTS: A dose-dependent increase of S-phase cells followed by decrement of G2M cell compartment was observed. The significant block of S-phase cells, however, was not always associated with @entity600 . The degree of cell-cycle disturbance was expressed more readily by the ratio G2M/S that demonstrated consistently the threshold character of both teratogenic and lethal effects. CONCLUSION: CP-induced @entity137 manifested by dose-dependent disturbance of cell-cycle resulted in an overall @entity308 of proliferation activity clearly associated with the occurrence of @entity600 and @entity204 . Although a non-significant @entity308 of mitotic activity appeared sufficient to produce @entity600 on Day 2, remarkably deeper disturbance was needed to interfere with the development of the embryos in more advanced stages. Changes in proliferation rate appear to be a primary and most important event in teratogenesis induced by general toxic agents.
