Cell cycle kinetics in fetal rat cerebral cortex: effects of prenatal treatment with ethanol assessed by a cumulative labeling technique with flow cytometry.
The effects of ethanol on the cell cycle kinetics of cortical precursor cells during the period of cortical neuronogenesis [between gestational day (G) 12 and G21] was systematically examined. Samples of dissociated cortical cells were harvested from the cerebral cortices of 13-, 15-, 17-, 19-, and 21-day-old fetuses. The fetuses were obtained from pregnant rats: (a) fed a liquid diet containing 6.7% (v/v) ethanol (Et) ad libitum, (b) pair-fed an isocaloric liquid control diet (Ct), or (c) fed chow and water (Ch) ad libitum. Before harvesting the cells, the fetuses were administered a series of 1-5 injections of bromodeoxyuridine (BrdU). The proportion of cells that incorporated the BrdU was assessed. Using these raw data, the S-phase length (Ts), total cell cycle length (Tc), and the growth fraction (GF; the fraction of the total population that was actively cycling) were determined with a cumulative labeling procedure. The Ts was approximately 8-9 hr, regardless of either the date of the injection or the dietary treatment of the dam. On the other hand, the Tc for the Ct- and Ch-treated rats increased over the gestational period. That is, the Tc was shortest on G13 and longest on G21. The Tc for Et-treated rats, however, did not change between G13 and G21. For the Ch- and Ct-treated groups, the GF decreased > 15-fold between G13 and G21. The decline (5-fold) for the Et-treated group over the same period, however, was not as great as it was for the Ct-treated fetuses.(ABSTRACT TRUNCATED AT 250 WORDS)