Poly human leukemia cells

Antimetabolites - Two reports on the metabolism of methotrexate (MTX) to 7-hydroxy-methotrexate (7-OH MTX) have appeared. The major metabolite of MTX in rabbits was found to be 7-OH MTX. The clearance of 7-OH MTX from plasma was slower than that of MTX itself. In a study of the uptake and metabolism of MTX in a MTX-sensitive human acute lymphoblastic leukemia cell line, MOLT4, it was shown that 7-OH MTX and MTX are converted to poly glutamates and that 7-OH MTX interferes with MTX accumulation and metabolism. Phase I clinical trials of 10-... 

Anderson MG, Scoggin KE, Simbulan-Rosenthal CM et al. Identification of poly(ADP-ribose) polymerase as a transcriptional coactivator of the human T-cell leukemia virus type 1 Tax protein, j Virol 2000 74(5) 2l69-2177. 

Kuo ML, Chau YP, Wang JH et al. Inhibitors of poly(ADP-ribose) polymerase block nitric oxide-induced apoptosis but not differentiation in human leukemia HL-60 cells. Biochem Biophys Res Commun 1996 219(2) 502-508. 

In Vivo Poly(ADP-ribose) Levels in Carcinogen Treated Human Promyelocytic Leukemia Cells... 

We have devised an activity gel procedure to recover the functional poly(ADP-ribose) polymerase catalytic activities after SDS-polyacrylamide gel electrophoresis [1]. Using this technique, we analyzed the catalytic polypeptides of this enzyme present in extracts obtained from a variety of organisms, belonging to a wide evolutionary scale. We also measured the enzyme in human lymphocytes before and after stimulation with mitogens and in human cells of different leukemia states. 

The exquisite sensitivity of resting lymphocytes to DNA damage and poly(ADP-ribose) polymerase activation may be due, in part, to a decreased capacity of the cells to synthesize NAD. Human lymphocytes possess an intact pyridine nucleotide cycle (10). The cells synthesize NAD from either nicotinamide or nicotinic acid, and they release nicotinamide as a by-product of ADP-ribosylation reactions. NMN pyrophosphorylase is the rate-limiting enzyme in NAD biosynthesis from nicotinamide, and the content of this enzyme in unstimulated human lymphocytes is quite low (9). We have examined the rate of NAD turnover in resting lymphocytes in order to quantitate the contribution of ADP-ribosylation to the overall consumption of NAD (10). In addition, we present here preliminary results of in vitro biochemical studies performed on malignant lymphocytes from patients with chronic lymphocytic leukemia (CLL), who were treated with 2-chlorodeoxyadenosine. 

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