Detail of "38819-10-2"

Reference

Characterization of arabinosylguanine resistance in a lymphoblastoid cell line

Characterization of arabinosylguanine resistance in a lymphoblastoid cell line. Shewach, Donna S.; Mitchell, Beverly S. (Med. Cent., Univ. Michigan, Ann Arbor, MI 48109, USA). Adv. Exp. Med. Biol., 195B(Purine Pyrimidine Metab. Man 5, Pt. B), 605-9 (English) 1986. CODEN: AEMBAP. ISSN: 0065-2598. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Using sensitive (MOLT-4 T lymphoblasts) and resistant (24B3) cells lines, it was shown that the cytotoxicity of arabinosylguanine (I) [38819-10-2] may be due to the accumulation of I-triphosphate (araGTP) [72490-81-4] in the sensitive cells; the amt. of araGTP in the resistant cells after incubation was much lower than that obsd. with the sensitive cells. Although I was found to be a substrate for purine nucleoside phosphorylase [9030-21-1] in human cells, the degrdn. of I by this enzyme was much slower than that obsd. for deoxyguanosine. The sensitivity of resistant 24B3 cells to ara C [147-94-4] was also examd. These cells were more sensitive to ara C than to I possibly because of different kinases which phosphorylated I and ara C to their resp. triphosphates. Thus, the sensitivity and resistance of cells to I appear to depend upon the levels of accumulation of araGTP in the cell.

Rhodamine 123 and flow cytometry to monitor the cytotoxic actions of nucleoside analogs in nondividing human lymphocytes

Rhodamine 123 and flow cytometry to monitor the cytotoxic actions of nucleoside analogs in nondividing human lymphocytes. Verhoef, Vernon; Ashmun, Richard; Fridland, Arnold (Dep. Biochem. Clin. Pharmacol., St. Jude Child. Res. Hosp., Memphis, TN 38101, USA). Anticancer Res., 6(5), 1117-21 (English) 1986. CODEN: ANTRD4. ISSN: 0250-7005. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Section cross-reference(s): 4 Human lymphocytes from the peripheral blood of normal individuals were used to compare the cytolytic actions of 2-chloro-2'-deoxyadenosine (2-Cl-d-Ado) [4291-63-8] and 9-b-D-arabinofuranosylguanine (ara-G) [38819-10-2]. Membrane integrity was ascertained by flow cytometric quantification of the cells' uptake of the fluorescent mitochondria-specific probe rhodamine 123 [62669-70-9]. Addn. of 10mM ara-G to lymphocyte cultures led to a progressive decline in the no. of cells that could assimilate rhodamine 123, and after 2 days exposure to drug less than 50% of the cells showed normal staining compared to untreated cells. 2-Cl-dAdo had similar cytotoxic effects at a 0.1 mM concn. Under the same conditions trypan blue revealed only a 10-20% toxic effect by these drugs. By using rhodamine 123 in combination with the vital stain propidium iodide, it was found that 90% of the cells with abnormal rhodamine 123 uptake also stained with propidium iodide. The changes in membrane permeability to fluorescent dyes correlated with the loss of lymphocyte ability to respond to the plant mitogen phytohemagglutinin. Apparently, rhodamine 123 is a more sensitive probe than trypan blue for ascertaining early loss of the membrane integrity of dying lymphocytes. Combined with flow cytometry, rhodamine 123 uptake represents a simple and rapid method for identifying the important biochem. events assocd. with the cytocidal and cytostatic effect of drugs against normal and leukemic cells.