43 research outputs found
The histone deacetylase inhibitor trichostatin A downregulates human MDR1 (ABCB1) gene expression by a transcription-dependent mechanism in a drug-resistant small cell lung carcinoma cell line model
Tumour drug-resistant ABCB1 gene expression is regulated at the chromatin level through epigenetic mechanisms. We examined the effects of the histone deacetylase inhibitor trichostatin A (TSA) on ABCB1 gene expression in small cell lung carcinoma (SCLC) drug-sensitive (H69WT) or etoposide-resistant (H69VP) cells. We found that TSA induced an increase in ABCB1 expression in drug-sensitive cells, but strongly decreased it in drug-resistant cells. These up- and downregulations occurred at the transcriptional level. Protein synthesis inhibition reduced these modulations, but did not completely suppress them. Differential temporal patterns of histone acetylation were observed at the ABCB1 promoter: increase in H4 acetylation in both cell lines, but different H3 acetylation with a progressive increase in H69WT cells but a transient one in H69VP cells. ABCB1 regulations were not related with the methylation status of the promoter −50GC, −110GC, and Inr sites, and did not result in further changes to these methylation profiles. Trichostatin A treatment did not modify MBD1 binding to the ABCB1 promoter and similarly increased PCAF binding in both H69 cell lines. Our results suggest that in H69 drug-resistant SCLC cell line TSA induces downregulation of ABCB1 expression through a transcriptional mechanism, independently of promoter methylation, and MBD1 or PCAF recruitment
Wire mesh sensor measurements of a co-current two-phase flow in a spent fuel pool-like rack
International audienceIncreased attention has been paid in the last decade to the Spent Fuel Pools (SFP) accident phenomenology. The DENOPI project conducted by the IRSN is part of this approach with the aim to gain knowledge in the SFP under loss of cooling or loss of coolant accident conditions and to better evaluate the safety margins. Questions are still pending regarding the issues of convective heat transfer under natural circulation due to a loss of cooling. For instance, the validation of computer codes for accident analysis in case of a natural circulation flow in a fuel assembly with boiling at atmospheric pressure requires additional experimental data. In that view, the MEDEA facility has been set up to study, inter alia, a co-current air/water flow in a SFP-like rack with a one meter height rod bundle. The pressure loss and void fraction are measured all along the fuel bundle using several pressure transducers. Besides, the void fraction and the bubble distribution at the outlet of the pool rack are obtained by means of a Wire Mesh Sensor (WMS)
3He mass spectrometry for very low-level measurement of organic tritium in environmental samples
International audienc
Helium isotopes in hydrothermal volcanic fluids of the Azores archipelago
International audienc
Assessment and interpretation of a round-robin exercise for organically bound tritium determination
Proceedings of the 2008 International Liquid Scintillation Conference, Davos, Switzerland, 25-30 May 2008International audienc
Towards speciation of organically bound tritium and deuterium: Quantification of non-exchangeable forms in carbohydrate molecules
International audienceAn original methodology to quantitatively explore exchangeability of hydrogen isotopes in carbohydrate molecules is proposed. To access the speciation of organically bound hydrogen isotopes, isotopic exchanges were carried out under a soft path regime in the vapor phase at 20°C with set (D,T/H) vapor pressure ratios. When steady states were reached, the fraction of exchangeable hydrogen of microcrystalline cellulose, alpha-cellulose and wheat grains were obtained and ranged from 13 to 31 % (versus a theoretical value of 30 %). In cellulose, and more specifically in microcrystalline cellulose, the molecular hydrogen bonds as well as the different conformations of the network seemed to decrease the hydroxyl groups of glucose units available for isotopic exchange. On the contrary, the assumed enzymatic hydrolysis of the constitutive molecules of wheat starch into low-molecular weight carbohydrate molecules enhanced the exchangeable pool. An average value of the activity between non-exchangeable organically bound tritium (NE-OBT) and non-exchangeable organically bound hydrogen was calculated for wheat grains, (T/H)_NE = 0.55 +- 0.03 Bq.g-1 of hydrogen atoms