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Dermatotoxic chemical stimulate of c-jun and c-fos transcription and AP-1 DNA binding in human keratinocytes.
Burleson FG; Simeonova PP; Germolec DR; Luster MI
Res Commun Mol Pathol Pharmacol 1996 Aug; 93(2):131-148
The effects of dermatotoxic chemicals on activator protein (AP1) DNA binding activity and c-jun and c-fos messenger RNA (mRNA) levels were examined in normal human epidermal keratinocytes. A phorbol-12- myristate-13-acetate (16561298) (PMA) dose of 10 nanograms per milliliter, a phenol (108952) dose of 1mg/ml, and a sodium-arsenite (7784465) concentration of 4 millimolar were added to cell cultures. Reverse transcription and polymerase chain reaction was performed with extracted mRNA. Primer sequences for interleukin-1alpha (IL1alpha), c-jun, c-fos, and glyceraldehyde-3-phosphate- dehydrogenase (G3PDH) were used. A video system was applied to the determination of relative changes in the mRNA transcripts. DNA binding reactions and the electrophoresis mobility shift assay were also conducted. Chemical treatment increased the detectable levels of c-fos mRNA in keratinocytes. PMA treatment induced the strongest and longest elevation in c-fos expression, which returned to control levels within 8 hours. The increases in c-fos expression caused by arsenic and phenol exposures decreased to control levels within 6 hours. Within 60 minutes of exposure to PMA, c-jun mRNA levels were elevated. Arsenic and phenol treatments increased c-jun expression at 4 hours postexposure. PMA, arsenic, and phenol treatments resulted similarly in the enhanced formation of an AP1 DNA binding complex. Compared to controls, treatment with PMA, arsenic, and phenol resulted in increases in IL1alpha gene expression by six fold, three fold, and two fold, respectively. Treatment with dermatotoxic chemicals did not alter G3PDH gene expression. The authors conclude that dermatotoxic chemical exposure increases the AP1 DNA binding activity and the stimulation of early/immediate genes.
NIOSH-Author; Mammalian-cells; Cell-cultures; Cellular-function; Toxic-effects; Cellular-reactions; Toxic-dose; In-vitro-study; Bioactivation; Molecular-biology
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Issue of Publication
Research Communications in Molecular Pathology and Pharmacology
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