Resistance to 6-thioguanine in spontaneously cycling and in mitogen-stimulated human peripheral lymphocytes.

Spontaneously cycling lymphocytes (in cell division in cultures without addition of phytohemagglutinin, PHA) go through the various phases of the first division with the same kinetics as PHA-stimulated cells. In samples from 10 referents, the frequency of spontaneously cycling lymphocytes varied from 8.9 X 10(-5)-9.5 X 10(-3) as indicated with autoradiography on cells in (S + G2) phase determined by flow sorting. In PHA-stimulated samples from the same persons the frequency of 6-thioguanine (TG)-resistant variants was between 4 X 10(-7) and 2.6 X 10(-6), which indicates that most of the spontaneously cycling cells were TG-sensitive. With lymphocytes from one of the referents it was found that: (i) in the presence of 2 X 10(-4) M TG, more than 97% of the spontaneously cycling cells were inhibited before or in early S phase, and (ii) when a flow cytometer was set to sort out TG-resistant cells in late S + G2 phase after 48 h incubation in medium with PHA, the contribution of TG-resistant cells from the spontaneously cycling fraction amounted to less than 2% of the total number of resistant cells.