Effects of Retinoic Acid Versus Dimethyl Sulfoxide on Friend Erythroleukemia Cell Growth. II. Induction of Quiescent, Nonproliferating Cells

Abstract

Treatment of Friend erythroleukemia (FL) cells in vitro with 10⁻⁷ to 10⁻⁷all-trans-retinoic acid (RA) leads to a concentration-dependent accumulation of a subpopulation of quiescent cells. This subpopulation, termed “Q-cells,” contained markedly reduced RNA and protein levels and had a cell cycle distribution with a predominance of cells in G₁ phase, which was nearly identical to that found in fully differentiated dimethyl sulfoxide (CAS:67-68-5; methyl sulfoxide)-induced FL cultures. The G₁ cells in this RA-induced subpopulation (G_1Q cells), though viable, did not enter S-phase, whereas the small percentage of Q-cells with S and G₂ DNA content progressed very slowly through the cycle. While the Q-cell population did not contain the differentiation-associated chromatin protein H1°, the cells did manifest a more condensed nuclear chromatin, altered sensitivity to acid denaturation, and reduced accessibility of the DNA in chromatin to acridine orange. The extent of chromatin condensation and the number of free ribosomes versus polysomes in RA-treated FL cells were intermediate between those in untreated and fully differentiated cells, whereas viral budding and the number of nucleoli remained unchanged from those seen in the untreated cell state. The non-Q-cell population in RA-treated cultures, termed “T” (transitional) cells, had an intermediate RNA and protein content and a cell cycle distribution similar to those of control cultures nearing the plateau phase of growth. In the absence of any late markers of differentiation, the Q-cell population was tentatively identified as a unique, quiescent cell population not previously described in the FL cell system.