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-robose)n. Interestingly, certain steroids which bind to the receptor but do not 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'-menthyl 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.

Agency
National Institute of Health (NIH)
Institute
Division of Cancer Biology And Diagnosis (NCI)
Type
Intramural Research (Z01)
Project #
1Z01CB008709-10
Application #
3963036
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
10
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Cancer Biology and Diagnosis
Department
Type
DUNS #
City
State
Country
United States
Zip Code