Home LiteratureArticle Details
PMID: 6184719 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Selective amplification of polymorphic dihydrofolate reductase gene loci in Chinese hamster lung cells.

Lewis JA, Davide JP, Melera PW

Abstract

A series of antifolate-resistant Chinese hamster lung sublines that overproduce either a Mr 20,000 or a Mr 21,000 class of dihydrofolate reductase (DHFR; tetrahydrofolate dehydrogenase; 5,6,7,8-tetrahydrofolate:NADP+ oxidoreductase, EC 1.5.1.3), known to contain amplified DHFR genes, has been analyzed by DNA and RNA transfer techniques. The results suggest that the Mr 20,000 and Mr 21,000 DHFRs are encoded by at least two polymorphic DHFR genes, both of which are expressed in drug-sensitive parental cells. In drug-resistant sublines only one of the two DHFR gene types is amplified, thus accounting for the overproduction of one or the other molecular weight class of DHFR. In addition to the known differences between the DHFRs whose overproduction they direct, these allelic genes differ in restriction endonuclease profiles and in the relative abundances of their multiple mRNA transcripts.

MeSH Terms
Animals Cell Line Cricetinae Cricetulus Drug Resistance Folic Acid Antagonists/pharmacology Gene Amplification Genes Lung Poly A/genetics Polymorphism, Genetic RNA/genetics RNA, Messenger Tetrahydrofolate Dehydrogenase/genetics
Chemicals
Folic Acid Antagonists RNA, Messenger Poly A RNA Tetrahydrofolate Dehydrogenase
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Lewis J A
Davide J P
Melera P W
References (23)
23 references, click to expand
  1. Cellular resistance to actinomycin D in Chinese hamster cells in vitro: cross-resistance, radioautographic, and cytogenetic studies.
    Cancer Res. 1970 Apr;30(4):1174-84 PMID: 5533992
  2. Membrane-mediated drug resistance and phenotypic reversion to normal growth behavior of Chinese hamster cells.
    J Natl Cancer Inst. 1975 Sep;55(3):671-80 PMID: 1159844
  3. Detection of specific sequences among DNA fragments separated by gel electrophoresis.
    J Mol Biol. 1975 Nov 5;98(3):503-17 PMID: 1195397
  4. Metaphase chromosome anomaly: association with drug resistance and cell-specific products.
    Science. 1976 Jan 16;191(4223):185-7 PMID: 942798
  5. RNA molecular weight determinations by gel electrophoresis under denaturing conditions, a critical reexamination.
    Biochemistry. 1977 Oct 18;16(21):4743-51 PMID: 911786
  6. Method for detection of specific RNAs in agarose gels by transfer to diazobenzyloxymethyl-paper and hybridization with DNA probes.
    Proc Natl Acad Sci U S A. 1977 Dec;74(12):5350-4 PMID: 414220
  7. Selective multiplication of dihydrofolate reductase genes in methotrexate-resistant variants of cultured murine cells.
    J Biol Chem. 1978 Mar 10;253(5):1357-70 PMID: 627542
  8. Amplified dihydrofolate reductase genes are localized to a homogeneously staining region of a single chromosome in a methotrexate-resistant Chinese hamster ovary cell line.
    Proc Natl Acad Sci U S A. 1978 Nov;75(11):5553-6 PMID: 281704
  9. Alleles of the fibroin gene coding for proteins of different lengths.
    Cell. 1979 Jun;17(2):407-13 PMID: 455471
  10. Gene amplification causes overproduction of the first three enzymes of UMP synthesis in N-(phosphonacetyl)-L-aspartate-resistant hamster cells.
    J Biol Chem. 1979 Sep 10;254(17):8679-89 PMID: 381311
  11. Correlation of dihydrofolate reductase elevation with gene amplification in a homogeneously staining chromosomal region in L5178Y cells.
    J Cell Biol. 1979 Nov;83(2 Pt 1):394-402 PMID: 500787
  12. The development of resistance to methotrexate in a mouse melanoma cell line. I. Characterisation of the dihydrofolate reductases and chromosomes in sensitive and resistant cells.
    Chromosoma. 1979;74(2):153-77 PMID: 510081
  13. Antifolate-resistant chinese hamster cells. Evidence from independently derived sublines for the overproduction of two dihydrofolate reductases encoded by different mRNAs.
    J Biol Chem. 1980 Jan 25;255(2):319-22 PMID: 7356612
  14. Antifolate-resistant Chinese hamster cells. Evidence for dihydrofolate reductase gene amplification among independently derived sublines overproducing different dihydrofolate reductases.
    J Biol Chem. 1980 Jul 25;255(14):7024-8 PMID: 7391066
  15. Tissue-specific expression of mouse-alpha-amylase genes: nucleotide sequence of isoenzyme mRNAs from pancreas and salivary gland.
    Cell. 1980 Aug;21(1):179-87 PMID: 6157477
  16. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose.
    Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201-5 PMID: 6159641
  17. Ovomucoid intervening sequences specify functional domains and generate protein polymorphism.
    Cell. 1980 Oct;21(3):681-7 PMID: 7438205
  18. Repetitive DNA sequences in methotrexate- and methasquin-sensitive and -resistant Chinese hamster cell lines.
    Biochem Genet. 1980 Aug;18(7-8):655-67 PMID: 6258555
  19. Molecular cloning of Chinese hamster dihydrofolate reductase-specific cDNA and the identification of multiple dihydrofolate reductase mRNAs in antifolate-resistant Chinese hamster lung fibroblasts.
    Nucleic Acids Res. 1981 Mar 25;9(6):1311-22 PMID: 6262725
  20. Amplification of the metallothionein-I gene in cadmium-resistant mouse cells.
    Proc Natl Acad Sci U S A. 1981 Apr;78(4):2110-4 PMID: 6941274
  21. Genetic polymorphisms and gene expression variations at enzyme loci in chinese hamster cell lines.
    Somatic Cell Genet. 1981 May;7(3):295-306 PMID: 7197402
  22. Gene amplification accompanies low level increases in the activity of dihydrofolate reductase in antifolate-resistant Chinese hamster lung cells containing abnormally banding chromosomes.
    J Cell Biol. 1982 Aug;94(2):418-24 PMID: 7107708
  23. Multiple forms of human dihydrofolate reductase messenger RNA. Cloning and expression in Escherichia coli of their DNA coding sequence.
    J Mol Biol. 1982 Apr 15;156(3):583-607 PMID: 6750132
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1982-11-00
Pages
6961-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC347254
Subset
IM
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]