Drugs which inhibit (ADP-ribose)n synthetase and decrease endogenous ADP-ribosylation of chromosomal proteins cause accumulation of mRNA for glucocorticoid sensitive genes. Considerable variations in the extent of accumulation have been observed during the course of this study. Thus, factors in addition to the total amount of nuclear (ADP-ribose)n are involved. Glucocorticoid agonists or partial agonists are more effective agonists in cells devoid of (ADP-ribose)n. Interestingly, certain steroids which bind to the receptor but do to normally induce genes are also very good agonists in these cells. We conclude that ADP-ribosylation of some essential protein(s), possibly the steroid receptor, influences expression of steroid-sensitive genes. Nicotinamide and its synthetic N'-methyl derivative induce maturation of cultured human promyelocytic leukemia HL60 cells. The actions of these compounds are synergistic with retinoic acid, another agent which induces maturation of these cells. N'- methylnicotinamide is converted into N'-methylnicotinamide adenine dinucleotide. This NAD analog may be the active intracellular compound in the cells. Thermal stress of cultured mouse mammary carcinoma cells results in a loss of basal and glucocorticoid-induced mouse mammary tumor virus (MMTV) RNA within about 60 min. Cycloheximide treatment prior to the temperature shift prevents loss of the RNA. A nuclease which is subject to a rapid turnover may be activated by the heat shock.
