Abstract：
:Insulin-exposed rat mammary cancer cells were flow sorted based on a c-myc reporter plasmid encoding a destabilized green fluorescent protein. Sorted cells exhibited gradual increases in c-myc levels. Cells overexpressing c-myc by only 10% exhibited phenotypic changes attributable to c-myc overexpression, such as cell cycle disturbances, increased cell size, and overexpression of the S6 ribosomal protein. Cells overexpressing c-myc by 70% exhibited additional phenotypic changes typical of c-myc overexpression, such as increased histone H3 phosphorylation, and reduced adherence. Sorted cells also exhibited overexpression of the IGF-1R, and slightly elevated expression of the IR. Increased susceptibility to the mitogenic effect of insulin was seen in a small proportion of the sorted cells, and insulin was more effective in activating the p44/42 MAPK pathway, but not the PI3K pathway, in the sorted cells than in the nonsorted cell population. To our knowledge, this is the first in vitro system allowing functional coupling between mitogenic signaling by a well-defined growth factor and gradual overexpression of the normal, endogenous c-myc gene. Thus, our flow-sorting approach provides an alternative modeling of the receptor-mediated carcinogenic process, compared to the currently used approaches of recombinant constitutive or conditional overexpression of oncogenic transmembrane receptor tyrosine kinases or oncogenic transcription factors.
journal_name
Arch Toxicoljournal_title
Archives of toxicologyauthors
Knudsen KJ,Nelander Holm GM,Krabbe JS,Listov-Saabye N,Kiehr B,Dufva M,Svendsen JE,Oleksiewicz MBdoi
10.1007/s00204-009-0463-6subject
Has Abstractpub_date
2009-12-01 00:00:00pages
1061-74issue
12eissn
0340-5761issn
1432-0738journal_volume
83pub_type
杂志文章abstract：:Regarding the cancer risk assessment of acrylamide (AA) it is of basic interest to know, as to what amount of the absorbed AA is metabolized to glycidamide (GA) in humans, compared to what has been observed in laboratory animals. GA is suspected of being the ultimate carcinogenic metabolite of AA. From experiments wit...
journal_title：Archives of toxicology
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journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s002040050326
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journal_title：Archives of toxicology
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journal_title：Archives of toxicology
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更新日期：2018-04-01 00:00:00
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journal_title：Archives of toxicology
pub_type： 杂志文章,评审
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journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-004-0586-8
更新日期：2004-11-01 00:00:00
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journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s002040050467
更新日期：1997-01-01 00:00:00
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journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF00353318
更新日期：1975-10-20 00:00:00
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journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF00290553
更新日期：1986-12-01 00:00:00
abstract：:Carbromal is metabolized extensively in humans. The major metabolites known to date are bromoethylbutyramide, ethylbutyrylurea and inorganic bromide. After ingestion of a therapeutic dose of 1.0 g carbromal (4.2 mmoles) by four healthy volunteers highest concentrations in serum were found to be for carbromal 30 mumole...
journal_title：Archives of toxicology
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doi：10.1007/BF00364653
更新日期：1978-06-16 00:00:00
abstract：:The aim of our study was to determine the period of maximum sensitivity for the induction of characteristic malformations with thalidomide (TH) in Himalayan rabbits. TH was administered orally in different doses (50, 100, 150 and 200 mg/kg) four times at 24-h intervals starting at 192 h of gestation. The malformations...
journal_title：Archives of toxicology
pub_type： 杂志文章
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更新日期：1987-07-01 00:00:00
abstract：:The mycotoxin deoxynivalenol (DON) has a high global prevalence in grain-based products. Biomarkers of exposure are detectable in most humans and farm animals. Considering the acute emetic and chronic anorexigenic toxicity of DON, maximum levels for food and feed have been implemented by food authorities. The tolerabl...
journal_title：Archives of toxicology
pub_type： 杂志文章
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更新日期：2019-07-01 00:00:00
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journal_title：Archives of toxicology
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更新日期：1993-01-01 00:00:00
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journal_title：Archives of toxicology
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更新日期：2005-01-01 00:00:00
abstract：:Age-related macular degeneration (AMD) is a late-onset retinal disease and the leading cause of central vision loss in the elderly. Degeneration of retinal pigment epithelial cells (RPE) is a crucial contributing factor responsible for the onset and progression of AMD. The toxic fluorophore N-retinyl-N-retinylidene et...
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journal_title：Archives of toxicology
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更新日期：2009-06-01 00:00:00
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journal_title：Archives of toxicology
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更新日期：2014-02-01 00:00:00
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journal_title：Archives of toxicology
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journal_title：Archives of toxicology
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更新日期：2018-05-01 00:00:00
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journal_title：Archives of toxicology
pub_type： 杂志文章
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更新日期：2015-09-01 00:00:00
abstract：:The neurological effects of four synthetic pyrethroids resmethrin, permethrin, cypermethrin, and deltamethrin have been investigated in the rat to establish whether there is a correlation between the clinical-functional status of the animal and peripheral nerve damage as measured biochemically. Neuromuscular dysfuncti...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF00294995
更新日期：1983-08-01 00:00:00
