TIME-COURSE OF PHORBOL-12-MYRISTATE-13-ACETATE (PMA)-INDUCED DOWN-REGULATION OF TOPOISOMERASE-II IN HUMAN LEUKEMIA-CELLS

The time course of the down-regulation of topoisomerase II associated with phorbol-induced differentiation was quantified in two human HL-60 leukemia cell lines. In the line sensitive to phorbol-induced differe ntiation (S cells), immunoreactive topoisomerase II levels did not beg in to fall until 12 hr following exposure of the cells to phorbol este r. Thereafter, levels declined over the next 36 hr. By contrast, phorb ol treatment of the phorbol ester tolerant cell line (PET cells) produ ced a transient decrease in topoisomerase II only to be followed by a recovery to pretreatment levels. The patterns of the alterations in to poisomerase II mRNA levels mirrored those of the alterations in immuno reactive topoisomerase II. Unexpectedly, nuclear run-on studies reveal ed that transcriptional start sites were not reduced in either cell li ne following their exposure to phorbol esters. These data suggest that the down-regulation of topoisomerase II is a consequence rather than a cause of phorbol-induced differentiation in HL-60 cells. Furthermore , this down-regulation is not mediated by a decrease in the number of topoisomerase II transcription sites.