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Effects of Calcitriol on Nuclear Transcription during Human HL-60 Promyelocytic Leukemia Cell Differentiation¹

Department of Pharmacology, The University of Michigan, Ann Arbor, Michigan 48109-0010

An HL-60 in vitro transcription assay was developed and used to monitor HL-60 human promyelocytic leukemia cell transcription during calcitriol-induced monocytic differentiation. Treatment of cells with calcitriol (50 nM) for 96 h produced a 48% reduction in total DNA-dependent RNA polymerase activity with a corresponding reduction in -amanitin-sensitive (RNA polymerase II) activity. Nuclei isolated from cells treated with the less efficacious vitamin D analogues, 24,25-dihydroxyvitamin D₃ and 1-hydroxyvitamin D₃, did not exhibit nuclear transcription that was significantly different from control nuclei. Transcription in nuclei isolated from calcitriol-treated cells was decreased by 40 to 50%, concomitant with monocytic differentiation, as assayed by acquisition of nitroblue tetrazolium reducing activity. Maximal decrease in transcription was achieved by 45 h postinduction, whereas expression of nitroblue tetrazolium reducing activity peaked at approximately 70 h, and decreased DNA synthesis was evident by 48 h. These observations suggest that calcitriol induction of HL-60 differentiation results in monocytes with reduced requirements for gene transcription and that transcription changes accompany expression of nitroblue tetrazolium reducing activity.

¹ This research was supported by NIH Grant CA 36507 and by grants from the Children's Leukemia Foundation of Michigan and the Cancer Research Institute of the University of Michigan.

² To whom requests for reprints should be addressed.

Received 9/17/85. Revised 3/ 6/86. Revised 6/27/86. Accepted 7/ 1/86.