Disease relevance of Adenine arabinoside

• Carbocyclic arabinofuranosyladenine (cyclaradine): efficacy against genital herpes in guinea pigs [1].
• Resistance to 9-beta-D-arabinofuranosyladenine in cultured leukemia L 1210 cells [2].
• S-adenosylhomocysteine catabolism and basis for acquired resistance during treatment of T-cell acute lymphoblastic leukemia with 2'-deoxycoformycin alone and in combination with 9-beta-D-arabinofuranosyladenine [3].
• The 6C3HED lymphosarcoma, a tumor cell line very sensitive to 9-beta-D-arabinofuranosyladenine (ara-A), and 6C3HED/ara-A, a line resistant to ara-A, were studied [4].
• The nucleoside 5'-diphosphate-L-1,2-dipalmitin derivatives of 1-beta-D-arabinofuranosylcytosine (ara-C), 9-beta-D-arabinofuranosyladenine (ara-A), and tubercidin have been synthesized, and their cytotoxicity has been evaluated against a mouse myeloma cell line (MPC-11) in vitro and against L1210 lymphoid leukemia both in vitro and in vivo [5].

High impact information on Adenine arabinoside

• Influence of 9-beta-D-arabinofuranosyladenine on total protein synthesis and on differential gene expression of unique proteins in the rodent malarial parasite Plasmodium berghei [6].
• Antiviral activity of a conjugate of adenine-9-beta-D-arabinofuranoside 5'-monophosphate and a 9 kDa fragment of arabinogalactan [7].
• In contrast, the phosphorylation of 9-beta-D-arabinofuranosyladenine was not affected, since it is mainly phosphorylated by adenosine kinase, which is not influenced by deoxyribonucleoside triphosphates [8].
• A series of nucleoside analogues (9-beta-D-arabinofuranosyladenine, N6-methyladenosine, 6-methylmercaptopurine ribonucleoside, tubercidin, ribavirin, and N-1-ribosyl-5-aminoimidazole-4-carboxamide riboside) also stimulated adenine nucleotide catabolism and increased AMP and IMP to various extents [9].
• 9-beta-D-Arabinofuranosyladenine (ara-A) is an inhibitor of DNA replication with antitumor and antiviral activity [10].

Chemical compound and disease context of Adenine arabinoside

• A cultured line of L1210 leukemia cells, designated L1210/ara-A, was selected for resistance to 9-beta-D-arabinofuranosyladenine (ara-A) by a series of 72-hr exposures to increasing concentrations of ara-A in the presence of 1 microM deoxycoformycin [2].
• The severity of herpetic keratitis induced by 9-(2-hydroxyethoxymethyl) guanine-resistant strains of herpes simplex virus was significantly reduced by cotherapy with 9-beta-D-arabinofuranosyladenine (ara-A) and 2-deoxycoformycin [11].
• Drug toxicity (measured by weight loss) was not detected in mice treated with cyclaradine or cyclaradine-5'-methoxyacetate at 750 mg/kg per day, whereas severe toxicity (weight loss of greater than or equal to 3 g) was observed in mice treated with vidarabine at an equivalent dose level [12].
• Erythro-9-(2-hydroxy-3-nonyl) Adenine alone and in combination with 9-beta-D-arabinofuranosyladenine in treatment of systemic herpesvirus infections in mice [13].
• Other drugs, including phosphonoformic acid, 9-beta-D-arabinofuranosyladenine, 5-iodo-2-deoxyuridine, and 1-beta-D-arabinofuranosylcytosine were active at concentrations previously shown to inhibit herpes simplex virus [14].

Biological context of Adenine arabinoside

• In in vivo mouse brain adenosine deaminase studies, inhibition of 9-beta-D-arabinofuranosyladenine deamination for periods of up to 24 hr was found after a single i.p. dose of 0.002 mmole/kg [15].
• Sensitization of noncycling human diploid cells to X-irradiation by pretreatment with 9-beta-D-arabinofuranosyladenine [16].
• The mechanism by which 9-beta-D-arabinofuranosyladenine produces cell death has been studied extensively, but the details remain controversial [17].
• This paper describes unusual sensitivity to bleomycin; resistance to aphidicolin, 9-beta-D-arabinofuranosyladenine, 1-beta-D-arabinofuranosylcytosine, and hydroxyurea; and a mutator phenotype as common phenotypes of two classes of previously reported mouse FM3A cell mutants with distinct biochemical defects [18].
• Delayed early transcription units were analyzed in similar studies by having 9-beta-D-arabinofuranosyladenine present during the experiment to block replication of the input irradiated genome [19].

Anatomical context of Adenine arabinoside

• Identification of the mechanism of activation of 9-beta-D-arabinofuranosyladenine in human lymphoid cells using mutants deficient in nucleoside kinases [20].
• The interactions between X-irradiation and 9-beta-D-arabinofuranosyladenine (ara-A) were studied in confluent, density-inhibited cultures of normal human diploid fibroblast cell strain AG1522. ara-A (0.1 to 3.0 x 10(-3) M) was added to the cultures either 2 or 24 h prior to irradiation [16].
• We found that WI-L2 X CEM hybrids and another T X B hybrid derived from fusion of the SB human B-cell line with CEM were 30- to 40-fold less sensitive to dAdo and about 10-fold less sensitive to the dAdo analogue 9-beta-D-arabinofuranosyladenine than was CEM, or about as resistant as were their B-cell parental lines [21].
• 9-beta-D-Arabinofuranosyladenine and ara-AMP represent neither direct mutagens nor premutagens as determined by the Salmonella-mammalian microsome mutagenicity test [22].
• Effects of 2'-deoxyadenosine, 9-beta-D-arabinofuranosyladenine, and related compounds on S-adenosyl-L-homocysteine hydrolase activity in synchronous and asynchronous cultured cells [23].

Associations of Adenine arabinoside with other chemical compounds

• This form of aberrant DNA synthesis was demonstrated to occur following direct inhibition of DNA replication by 1-beta-D-arabinofuranosylcytosine or 9-beta-D-arabinofuranosyladenine or after indirect inhibition with cycloheximide [24].
• Addition of 2'-deoxycoformycin to cell culture fluids enhanced the activity of 9-beta-D-arabinofuranosyladenine 5'-O-methylphosphate suggesting conversion to an adenosine deaminase-sensitive intermediate, presumably ara-A [25].
• S-adenosylhomocysteine and S-adenosylhomocysteine hydrolase in various tissues of mice given injections of 9-beta-D-arabinofuranosyladenine [26].
• The relative cytotoxicity of 9-beta-D-arabinofuranosyladenine and 9-beta-D-arabinofuranosyladenine 5'-monophosphate (ara-AMP) were compared using wild-type and adenosine kinase (AK)-deficient baby hamster kidney somatic cell mutants [27].
• Fludarabine phosphate (NSC 312878), an adenosine deaminase resistant analogue of 9-beta-D-arabinofuranosyladenine, has entered clinical trials [28].

Gene context of Adenine arabinoside

• Inactivation of S-adenosylhomocysteine hydrolase by 9-beta-D-arabinofuranosyladenine in intact cells [29].
• TPA-treated cells became resistant to the cytotoxic effects of 1-beta-D-arabinofuranosylcytosine (Ara-C), 9-beta-D-arabinofuranosyladenine (Ara-A), and 2-chlorodeoxyadenosine [30].
• On an equimolar basis, ara-AMP was consistently less cytotoxic than was 9-beta-D-arabinofuranosyladenine to wild-type and AK-deficient baby hamster kidney mutant cells [27].
• Reactivation of S-adenosylhomocysteine hydrolase activity in cells exposed to 9-beta-D-arabinofuranosyladenine [31].
• The findings demonstrate that 9-beta-D-arabinofuranosyladenine is incorporated into the elongating DNA strand by DNA polymerase-beta [10].

Analytical, diagnostic and therapeutic context of Adenine arabinoside

• After treatment of mice with 9-beta-D-arabinofuranosyladenine 5'-formate, intracellular levels of the 5'-triphosphate of 9-beta-D-arabinofuranosylfluoroadenine in leukemia cells were more than 10 times higher in L1210/0 cells than in L1210/ara-C cells [32].
• To facilitate pharmacokinetic studies on cyclaradine, an automated column-switching high-performance liquid chromatographic (HPLC) method was developed for the determination of cyclaradine in serum [33].
• Drug targeting in antiviral chemotherapy. A chemically stable conjugate of 9-beta-D-arabinofuranosyl-adenine 5'-monophosphate with lactosaminated albumin accomplishes a selective delivery of the drug to liver cells [34].
• The metabolism of 9-beta-D-arabinofuranosyladenine (AraA) to arabinofuranosyladenine 5'-triphosphate (AraATP), an inhibitor of DNA synthesis, in mouse leukemia cells was examined by means of high-pressure liquid chromatography [35].

References