Title of article :
HIV protease inhibitors block oral epithelial cell DNA synthesis
Author/Authors :
Danaher، نويسنده , , Robert J. and Wang، نويسنده , , Chunmei and Roland، نويسنده , , Andrew T. and Kaetzel، نويسنده , , Charlotte S. and Greenberg، نويسنده , , Richard N. and Miller، نويسنده , , Craig S.، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2010
Abstract :
Objectives
etroviral therapy regimens that include HIV protease inhibitors (PIs) are associated with diverse adverse effects including increased prevalence of oral warts, oral sensorial deficits and gastrointestinal toxicities suggesting that PIs may perturb epithelial cell biology. To test the hypothesis that PIs could affect specific biological processes of oral epithelium, the effects of these agents were evaluated in several oral epithelial cell-lines.
y and immortalized oral keratinocytes and squamous carcinoma cells of oropharyngeal origin were cultured in the presence of pharmacologically relevant concentrations of PIs. Their affects on cell viability, cytotoxicity and DNA synthesis were assessed by enzymatic assays and incorporation of 5-bromo-2′-deoxyuridine (BrdU) into DNA.
s
ity of primary and immortalized oral keratinocytes as well as squamous carcinoma cells of oropharyngeal origin was significantly reduced by select PIs at concentrations found in plasma. Of the seven PIs evaluated, nelfinavir was the most potent with a mean 50% inhibitory concentration [IC50] of 4.1 μM. Lopinavir and saquinavir also reduced epithelial cell viability (IC50 of 10–20 μM). Atazanavir and ritonovir caused minor reductions in viability, while amprenavir and indinavir were not significant inhibitors. The reduced cell viability, as shown by BrdU incorporation assays, was due to inhibition of DNA synthesis rather than cell death due to cytotoxicity.
sion
PIs retard oral epithelial cell proliferation in a drug and dose-dependent manner by blocking DNA synthesis. This could account for some of their adverse effects on oral health.
Keywords :
Protease inhibitors , Viability , HAART , epithelial cells
Journal title :
Archives of Oral Biology
Journal title :
Archives of Oral Biology