Genetic control of drug resistance: Assignment ofama-1 to Chinese hamster chromosome 7, confirmation of assignment of genes coding for TK, GALK, and ACP to chromosome 7, and tentative assignment of TPI to chromosome 8

1983 ◽  
Vol 9 (2) ◽  
pp. 235-248 ◽  
Author(s):  
Michele Roberts ◽  
George A. Scangos ◽  
John T. Hart ◽  
Frank H. Ruddle
2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Victoria I. Turilova ◽  
Tatyana S. Goryachaya ◽  
Tatiana K. Yakovleva

Abstract Background Chinese hamster ovary cell lines, also known as CHO cells, represent a large family of related, yet quite different, cell lines which are metabolic mutants derived from the original cell line, CHO-ori. Dihydrofolate reductase-deficient DXB-11 cell line, one of the first CHO derivatives, serves as the host cell line for the production of therapeutic proteins. It is generally assumed that DXB-11 is identical to DUKX or CHO-DUK cell lines, but, to our knowledge, DXB-11 karyotype has not been described yet. Results Using differential staining approaches (G-, C-banding and Ag-staining), we presented DXB-11 karyotype and revealed that karyotypes of DXB-11 and CHO-DUK cells have a number of differences. Although the number of chromosomes is equal—20 in each cell line—DXB-11 has normal chromosomes of the 1st and 5th pairs as well as an intact chromosome 8. Besides, in DXB-11 line, chromosome der(Z9) includes the material of chromosomes X and 6, whereas in CHO-DUK it results from the translocation of chromosomes 1 and 6. Ag-positive nucleolar organizer regions were revealed in the long arms of chromosome del(4)(q11q12) and both chromosome 5 homologues, as well as in the short arms of chromosomes 8 and add(8)(q11). Only 19 from 112 (16.96%) DXB-11 cells display identical chromosome complement accepted as the main structural variant of karyotype. The karyotype heterogeneity of all the rest of cells (93, 83.04%) occurs due to clonal and nonclonal additional structural rearrangements of chromosomes. Estimation of the frequency of chromosome involvement in these rearrangements allowed us to reveal that chromosomes 9, der(X)t(X;3;4), del(2)(p21p23), del(2)(q11q22) /Z2, der(4) /Z7, add(6)(p11) /Z8 are the most stable, whereas mar2, probably der(10), is the most unstable chromosome. A comparative analysis of our own and literary data on CHO karyotypes allowed to designate conservative chromosomes, both normal and rearranged, that remain unchanged in different CHO cell lines, as well as variable chromosomes that determine the individuality of karyotypes of CHO derivatives. Conclusion DXB-11and CHO-DUK cell lines differ in karyotypes. The revealed differential instability of DXB-11 chromosomes is likely not incidental and results in karyotype heterogeneity of cell population.


1985 ◽  
Vol 39 (2) ◽  
pp. 150-153 ◽  
Author(s):  
H. Brocas ◽  
J. Szpirer ◽  
R.V. Lebo ◽  
G. Levan ◽  
C. Szpirer ◽  
...  

1984 ◽  
Vol 38 (4) ◽  
pp. 257-264 ◽  
Author(s):  
F.A. Ray ◽  
M.F. Bartholdi ◽  
P.M. Kraemer ◽  
L.S. Cram

1975 ◽  
Vol 17 (4) ◽  
pp. 503-515 ◽  
Author(s):  
Victor Ling

Independent colchicine-resistant (CHR) mutants of Chinese hamster ovary cells displaying reduced permeability to colchicine have been isolated. A distinguishing feature of these membrane-altered mutants is their pleiotropic cross-resistance to a variety of unrelated compounds. Genetic characterization of the CHR lines indicates that colchicine resistance and cross-resistance to other drugs are of a dominant nature in somatic cell hybrids. Revertants of CHR have been isolated which display decreased resistance to colchicine and a corresponding decrease in resistance to other drugs. These results strongly suggest that colchicine resistance and the pleiotropic cross-resistance are the result of the same mutation(s). Biochemical studies indicate that although colchicine is transported into our cells by passive diffusion, no major alterations in the membrane lipids could be detected in mutant cells. However, there appears to be an energy-dependent process in these cells which actively maintains a permeability barrier against colchicine and other drugs. The CHR cells might be altered in this process. A new glycoprotein has been identified in mutant cell membranes which is not present in parental cells, and is greatly reduced in revertant cells. A model for colchicine-resistance is proposed which suggests that certain membrane proteins such as the new glycoprotein of CHR cells, are modulators of membrane fluidity (mmf proteins) whose molecular conformation regulates membrane permeability to a variety of compounds and that the CHR mutants are altered in their mmf proteins. The possible importance of the CHR cells as models for investigating aspects of chemotherapy related to drug resistance is discussed.


1991 ◽  
Vol 19 (3) ◽  
pp. 278S-278S ◽  
Author(s):  
SIOBHAN McCLEAN ◽  
RICHARD D. H. WHELAN ◽  
LOUISE K. HOSKING ◽  
BRIDGET T. HILL

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3653-3653
Author(s):  
Rami Khoriaty ◽  
Lukasz P. Gondek ◽  
Bartlomiej P Przychodzen ◽  
Theodore Ghazal ◽  
Abdo Haddad ◽  
...  

Abstract Introduction: The myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic stem cell disorders. Ringed sideroblasts (RS) are found in the following subclasses of MDS: refractory anemia with ringed sideroblasts (RARS), refractory cytopenia with multilineage dysplasia and ringed sideroblasts (RCMD-RS), and refractory anemia with ringed sideroblasts associated with marked thrombocytosis (RARS-T). The objective of this study was to evaluate the use of single nucleotide polymorphism (SNP) arrays (SNP-A) in patients with MDS and RS and specifically to compare chromosomal abnormalities detected by metaphase karyotyping (MC) with those detected using high-resolution SNP based karyotyping (which can detect unbalanced genomic lesions in addition to copy-neutral loss of heterozygozity) and to conduct a disease association analysis using the SNP-A. Methods: We reviewed the electronic records of patients with MDS and RS seen at our institution between 2002 and 2008. DNA was extracted using the Puregene DNA Purification Kit. Gene Chip Mapping 250K Assay Kit (Affymetrix) was used. Signal intensity and genotype calls were analyzed using CNAG v.3.0. For the disease association analysis, the Fisher’s p-value was used to compare SNPs found in patients with MDS and RS versus 150 normal controls. Results: 83 patients with MDS who have RS were identified. 40 (48%) had RARS, 25 (30%) had RCMD-RS, and 18 (22%) had RARS-T. The mean age of these patients was 70.7 years, 53 patients (64%) were males, and 70 (84%) were Caucasian. Of those 83 patients, 45 had available DNA for SNP analysis, 23 (51%) of whom had RARS, 11 (24%) had RCMD-RS, and 11 (24%) had RARS-T. The mean age of these 45 patients was 69.9 years, 29 (64%) were males, and 39 (87%) were Caucasian. By MC, 20/45 (44.5%) patients had abnormal karyotypes and 25/45 (55.5%) patients had normal karyotypes. Using SNP-A, chromosomal abnormalities including UPD were identified in 29/45 (64.5%) of patients. Of the 25 pts who had normal karyotypes by MC, 11 (44%) had abnormal karyotypes by SNP-A. The chromosomal distributions of the lesions detected by MC were as follows: chromosome 5 (18.4%), chromosome 7 (15.8%), chromosome 8 (13.1%), chromosome 17, 18, 19, 20, 21 (5.2% in each), and others (26.3 % in total). The distribution of chromosomal lesions detected by SNP-array analysis (excluding UPD) was as follows: chromosome 8 (18.7 %), chromosome 5 (14.6%), chromosome 7 (12.5%), chromosome 17 (10.4%), chromosome 20 (8.3%), chromosome 4 (6.2%), chromosomes 2, 3, 13, 22 (4.1% each), and others (12.5% in total). UPD was found in 12/45 (26.7%) patients mostly affecting chromosome 1 (27.8%). A large number of SNPs were found to be significantly more prevalent in patients with MDS with RS than in controls (with p-value < 0.0001). Genes within 50 kb from these SNPs were scrutinized. At least 11 of those genes (RP1, LIMD1, CHL1, ATP6V1F, TEAD2, SPTLC2, CDH13, DIAPH2, DLEU2, FAM10A4, TRPM8) are known to be related to cancer in the literature. Given that karyotypic abnormalities were more prevalent in chromosomes 8, 5, and 7, we looked specifically at the SNPs in those chromosomes which were significantly associated with disease (rs 409429, rs 446153, rs 453186 and rs 509273 in chromosome 8; rs6891109 in chromosome 5; and rs6970371 in chromosome 7). The genes within 50 kb of these SNPs that are known to be associated with cancer are: RP1 in chromosome 8 (colon cancer), and ATP6V1F in chromosome 7 (prostate cancer). Conclusion: This study shows that SNP-A based karyotyping is a useful tool for karyotyping and can detect more chromosomal abnormalities than MC (64.5 versus 44.5%, odds ratio 1.45). We also found that about half of the patients who had normal karyotypes by MC were found to have karyotypic abnormalities by SNP-A. In addition, we show multiple candidate genes that could be important in the pathogenesis of MDS with RS.


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