Mammalian Cell Line Selection Strategies for High-Producers

Several commercially available pharmaceutical compounds have been shown to block the I Krcurrent of the cardiac action potential. This effect can cause a prolongation of the electrocardiogram QTinterval and a delay in ventricular repolarization. The Food and Drug Administration recommends that all new potential drug candidates be assessed for I Krblock to avoid a potentially lethal cardiac arrhythmia known as torsades de pointes. Direct compound interaction with the human ether-a-go-go– related gene (hERG) product, a delayed rectifier potassium channel, has been identified as a molecular mechanism of I Kr block. One strategy to identify compounds withh ERGliability is to monitor hERGcurrent inhibition using electrophysiology techniques. The authors describe the Ion Works HT ™instrument as a tool for screening cell lines expressing hERG channels. Based on current amplitude and stability criteria, a cell line was selected and used to perform a 300-compound screen. The screen was able to identify compounds with hERG activity within projects that spanned different therapeutic areas. The cell line selection and optimization, as well as the screening abilities of the Ion Works HT ™system, provide a powerful means of assessinghERGactive compounds early in the drug discovery pipeline.

Download Full-text

Putrescine and related amines as growth factors for a mammalian cell line

Biochemical and Biophysical Research Communications ◽

10.1016/0006-291x(63)90206-7 ◽

1963 ◽

Vol 14 (1) ◽

pp. 34-38 ◽

Cited By ~ 96

Author(s):

Richard G. Ham

Keyword(s):

Growth Factors ◽

Cell Line ◽

Mammalian Cell ◽

Mammalian Cell Line

Download Full-text

Biological Studies of a Baculovirus in a Mammalian Cell Line

Intervirology ◽

10.1159/000149143 ◽

1980 ◽

Vol 13 (6) ◽

pp. 331-341 ◽

Cited By ~ 29

Author(s):

Arthur H. Mclntosh ◽

Rebecca Shamy

Keyword(s):

Cell Line ◽

Mammalian Cell ◽

Mammalian Cell Line ◽

Biological Studies

Download Full-text

A mammalian cell line deficient in activity of the DNA repair enzyme 5-hydroxymethyluracil-DNA glycosylase is resistant to the toxic effects of the thymidine analog 5-hydroxymethyl-2'-deoxyuridine

Molecular and Cellular Biology ◽

10.1128/mcb.12.12.5536-5540.1992 ◽

1992 ◽

Vol 12 (12) ◽

pp. 5536-5540

Author(s):

R J Boorstein ◽

L N Chiu ◽

G W Teebor

Keyword(s):

Dna Repair ◽

Cell Line ◽

Mammalian Cell ◽

Dna Glycosylase ◽

Mammalian Cell Line ◽

Repair Enzyme ◽

Thymidine Analog ◽

Large Numbers ◽

Mechanism Of Toxicity ◽

Base Excision

We isolated a mutant mammalian cell line lacking activity for the DNA repair enzyme 5-hydroxymethyluracil-DNA glycosylase (HmUra-DNA glycosylase). The mutant was isolated through its resistance to the thymidine analog 5-hydroxymethyl-2'-deoxyuridine (HmdUrd). The mutant incorporates HmdUrd into DNA to the same extent as the parent line but, lacking the repair enzyme, does not remove it. The phenotype of the mutant demonstrates that the toxicity of HmdUrd does not result from substitution of thymine in DNA by HmUra but rather from the removal via base excision of large numbers of HmUra residues in DNA. This finding elucidates a novel mechanism of toxicity for a xenobiotic nucleoside. Furthermore, the isolation of this line supports our hypothesis that the enzymatic repairability of HmUra derives not from its formation opposite adenine via the oxidation of thymine, but rather from its formation opposite guanine as a product of the oxidation and subsequent deamination of 5-methylcytosine.

Download Full-text