Loss of the MYC gene amplified in human HL-60 cells after treatment with inhibitors of poly(ADP-ribose) polymerase or with dimethyl sulfoxide.
In HL-60 cells, a human promyelocytic leukemia cell line, the human c-myc gene, designated MYC, is amplified about 16-fold. On differentiation of the HL-60 cells into granulocytes induced by several inhibitors of poly(ADP-ribose) polymerase [NAD+ poly(adenosine diphosphate D-ribose)ADP-D-ribosyltransferase, EC 2.4.2.30] including benzamide, nicotinamide, coumarin, and 4-hydroxyquinazoline or dimethyl sulfoxide, some MYC loss was observed. In contrast, benzoic acid, a noninhibitory analogue of benzamide, did not induce either granulocytic differentiation or loss of MYC. Loss of MYC seems to be associated with granulocytic differentiation because the time course of its loss was similar to that of appearance of nitroblue tetrazolium-positive cells, mature granulocytes, and its loss was not observed on differentiation of HL-60 cells into macrophages induced by phorbol 12-myristate 13-acetate or teleocidin. The loss of MYC is not the reason for the down regulation of MYC expression observed within 1 hr after addition of inducers, since the loss of MYC was not detected by 1-day treatment with inducers.
Shima
H
H
Carcinogenesis Division, National Cancer Center Research Institute, Tokyo, Japan.
Nakayasu
M
M
Aonuma
S
S
Sugimura
T
T
Nagao
M
M
D001549:Benzamides / Q000494:pharmacology; D015139:Blotting, Southern; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D003374:Coumarins / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D005784:Gene Amplification; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics; D009536:Niacinamide / Q000494:pharmacology; D009693:Nucleic Acid Hybridization; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc; D011519:Proto-Oncogenes / Q000187:drug effects*; D011799:Quinazolines / Q000494:pharmacology; D052999:Quinazolinones; D012334:RNA, Neoplasm / Q000187:drug effects / Q000235:genetics
D001549:Benzamides; D003374:Coumarins; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D011799:Quinazolines; D052999:Quinazolinones; D012334:RNA, Neoplasm; D009536:Niacinamide; C037689:benzamide; C061339:4-hydroxyquinazoline; C030123:coumarin; D004121:Dimethyl Sulfoxide