2-Aminobenzamide, an inhibitor of ADP-ribosylation, antagonizes induced DNA hypomethylation during differentiation of murine Friend erythroleukemia cells by N'-methylnicotinamide.
The ADP-ribose synthesis inhibitor 2-aminobenzamide was found to reduce the induction of haemoglobin synthesis in murine Friend erythroleukemia cells, cultured continuously for 96 h with 5 mM N'-methylnicotinamide, with over 50% inhibition at equimolar doses. 2-Aminobenzamide was optimally effective as an inhibitor of differentiation if present only during the time period 24-48 h after initial N'-methylnicotinamide exposure. A transient, genome-wide DNA hypomethylation accompanies induction by N'-methylnicotinamide. Although 2-aminobenzamide does not seem to affect normal DNA methylation in cultured cells, the observed DNA hypomethylation in cells cultured for 24 h with 5 mM N'-methylnicotinamide was antagonized over 50% by equimolar 2-aminobenzamide. We suggest that ADP-ribosylation has a positive modulatory role in erythroid differentiation, and possibly in the process(es) leading to DNA hypomethylation following inducer exposure.
Kuykendall
J R
JR
Cancer Research Laboratory, Veterans Administration Medical Center, Memphis, TN 38104.
Cox
R
R
D000246:Adenosine Diphosphate Ribose / Q000096:biosynthesis*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D004273:DNA, Neoplasm / Q000187:drug effects*; D005622:Friend murine leukemia virus; D006418:Heme / Q000096:biosynthesis; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism* / Q000473:pathology; D008745:Methylation; D051379:Mice; D009536:Niacinamide / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
D004273:DNA, Neoplasm; D062367:ortho-Aminobenzoates; D000246:Adenosine Diphosphate Ribose; D009536:Niacinamide; D006418:Heme; C000219:anthranilamide; C008472:N-methylnicotinamide