Disease relevance of Oua1

• These cells were used as targets in a series of assays designed to measure oncogenic transformation, mutation to ouabain resistance, cytotoxicity, and induction of cytogenetic changes, as evidenced by chromosomal aberrations and sister chromatid exchange [1].
• The tumour promoter TPA does not affect mutation to ouabain resistance in L5178Y mouse lymphoma cells [2].
• From among a series of stable, aphidicolin-resistant mutant strains of mouse teratocarcinoma, derived from a multipotent parental line (PSA-1-80), three were selected for further study on the basis of their comparatively high degrees of resistance and elevated frequencies of spontaneous forward mutation to 6-thioguanine and ouabain resistance [3].

High impact information on Oua1

• We show that the level of expression of either the ada or the ogt AT gene in C3H/10T1/2 cells directly correlates with protection against mutation to ouabain resistance by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) [4].
• DNA prepared from ouabain-resistant mouse cells was able to transform ouabain-sensitive CV-1 cells to ouabain resistance after DNA-mediated gene transfer [5].
• This plasmid was able to transform wild-type CV-1 cells to ouabain resistance at a frequency of about 10 cells per ng of DNA [5].
• The murine DNA fragment responsible for ouabain resistance was detected on the background of CV-1 DNA by virtue of a repetitive DNA sequence element that reacts positively with a mouse repeat DNA clone [5].
• The transformable mouse embryo fibroblast cell line C3H10T 1/2 C18 has been employed to study the induction by the carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) of morphological transformation and mutation to ouabain resistance throughout the cell cycle [6].

Chemical compound and disease context of Oua1

• Microtitration methods for assaying cell survival and mutation frequency to ouabain resistance, 6-thioguanine resistance and 1-beta-D-arabinofuranosyl cytosine resistance in L5178Y mouse lymphoma cells were compared to the standard agar cloning technique [7].

Biological context of Oua1

• We postulate that the "ouabain resistance gene" is important in the early selection process on ouabain but that the permanent ouabain-resistant phenotype is due to a stable mutation in one allele of the alpha-subunit of the Na,K-ATPase [8].
• Transfection of primate cells with a 6.4-kilobase murine genomic DNA fragment (called ouabain resistance gene or MOR6.5) has been shown previously to confer ouabain resistance (Levenson, R., Racaniello, V., Albritton, L., and Housman, D. (1984) Proc. Natl. Acad. Sci. U.S.A. 81, 1489-1493) [9].
• A murine genomic DNA fragment amplifies ouabain-induced Na,K-ATPase alpha/beta-subunit mRNA up-regulation and confers ouabain resistance [9].
• Assignment of the gene governing cellular ouabain resistance to Mus musculus chromosome 3 using human/mouse microcell hybrids [10].
• Differential cell cycle phase specificity for neoplastic transformation and mutation to ouabain resistance induced by N-methyl-N'-nitro-N-nitrosoguanidine in synchronized C3H10T 1/2 C18 cells [6].

Anatomical context of Oua1

• Chemical carcinogens induce mutations to ouabain resistance in the transformable mouse fibroblast cell line C3H/10T1/2 Cl 8 [11].
• Chemical carcinogens produce mutations to ouabain resistance in transformable C3H/10T1/2 Cl 8 mouse fibroblasts [11].
• Reduced ouabain inhibition of Na,K-activated adenosine triphosphatase in cultured cell recipients of the ouabain-resistance gene [12].
• When expressed in HeLa cells, this mutated sheep alpha 1 construct, like the rat/sheep chimera, was able to confer ouabain resistance to these cells [13].
• The mutagenic response at the ouabain resistance locus in T cells of mice exposed to N-ethyl-N-nitrosourea parallels the response at the Hprt locus and correlates with mutation target size [14].

Associations of Oua1 with chemical compounds

• Using cloned cells from three mouse tumors with differing metastatic potential, we determined the spontaneous mutation rates of cells with low or high metastatic capacities with respect to the selective genetic markers, 6-thiopurine resistance or ouabain resistance, or both [15].
• Ouabain resistance was induced by nitrosoguanidine, but not by ICR 191 [16].
• In contrast, induction of ouabain-resistant colonies was at a minimum at the time of maximal induction of transformation, and peak induction of ouabain resistance did not occur until 16-18 hr after release from the isoleucine block, when cells were in late S phase [6].
• On treatment of cells in suspension with N4-aminocytidine, the mutation to ouabain resistance was induced [17].
• PbCrO4 did not induce mutation to either 6-thioguanine or ouabain resistance but did induce a reproducible dose-dependent, low frequency of focus formation in 10T1/2 cells [18].

Other interactions of Oua1

• Other widely used systems depend on selecting for ouabain resistance, which is dominant and results from a change in the sodium/potassium ATPase activity, or on selecting for thymidine kinase mutants in heterozygous Tk+/Tk- mouse cells [19].
• In an assay for mutation to ouabain resistance in 10T 1/2 cells, which detects base substitution mutations but not frameshift mutations, 5-AzaCR and 6-azacytidine were not significantly mutagenic [20].
• Furthermore, our results suggest a linkage of the biochemical events underlying ouabain resistance and expression of differentiation phenotypes in the mouse neuroblastoma cells [21].

Analytical, diagnostic and therapeutic context of Oua1

• Molecular cloning of the mouse ouabain-resistance gene [5].
• After treatment with various concentrations of N-NO-2-FAA, ouabain resistance (ouar) was induced in C3H10T1/2 cells, while both ouar and 6-thioguanine resistance (6-TGr) were induced in CHO cells [22].
• Dose fractionation of a direct-acting chemical carcinogen, the alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), was studied for its concurrent effects on survival, DNA damage and repair, ouabain resistance (Ouar) mutations and neoplastic transformation, in the mouse embryo cell line BALB/3T3 C1A31-1-1 [23].

References