Radiation damage to a DNA-binding protein. Combined circular dichroism and molecular dynamics simulation analysis.

The E. coli lactose operon, the paradigm of gene expression regulation systems, is the best model for studying the effect of radiation on such systems. The operon function requires the binding of a protein, the repressor, to a specific DNA sequence, the operator. We have previously shown that upon irradiation the repressor loses its operator binding ability. The main radiation-induced lesions of the headpiece have been identified by mass spectrometry. All tyrosine residues are oxidized into 3,4-dihydroxyphenylalanine (DOPA). In the present study we report a detailed characterization of the headpiece radiation-induced modification. An original approach combining circular dichroism measurements and the analysis of molecular dynamics simulation of headpieces bearing DOPA-s instead of tyrosines has been applied. The CD measurements reveal an irreversible modification of the headpiece structure and stability. The molecular dynamics simulation shows a loss of stability shown by an increase in internal dynamics and allows the estimation of the modifications due to tyrosine oxidation for each structural element of the protein. The changes in headpiece structure and stability can explain at least in part the radiation-induced loss of binding ability of the repressor to the operator. This conclusion should hold for all proteins containing radiosensitive amino acids in their DNA-binding site.

[Accelerated partial breast irradiation: a concept to individualize treatment in breast cancer]. / Irradiation partielle et accélérée du sein: un concept pour une individualisation thérapeutique dans le cancer du sein.

Whole breast irradiation delivering an equivalent dose of 50 Gy in 5 weeks, followed by a 10 to 16 Gy-boost to the tumor bed is the standard of care after breast-conserving surgery for early-breast cancer. Accelerated partial breast irradiation (APBI) is currently under investigations in large multi-institutional, prospective, randomized trials to objectively address the critical endpoints of treatment efficacy, toxicity and cosmesis. Patient's selection for this new approach is crucial to individualise treatments and define the subgroups of patients who will really benefit from APBI in terms of quality of life without decreasing long-term results of the disease control and cosmesis. In this review, we will discuss the patients' profiles selection for APBI regarding their general and tumor criteria. The differences between APBI techniques either performed intra or post operatively will be also discussed.

[Partial breast irradiation: high dose rate peroperative brachytherapy technique using the MammoSite]. / Irradiation partielle du sein: technique de curiethérapie de haut débit de dose après l'implantation peropératoire du dispositif MammoSite.

In the conservative management of breast cancer, radiation therapy delivering 45 to 50 Gy to the whole breast, in 4.5 to 5 weeks, followed by a booster dose of 10 to 20 Gy is the standard of care. Based on the numerous studies which have reported that the local recurrences occurs within and surrounding the primary tumor site and in order to decrease the treatment duration and its morbidity, partial breast irradiation using several techniques has been developed. Partial irradiation may be considered as an alternative local adjuvant treatment for selected patients with favorable prognostic factors. Using external beam radiation therapy, the 3D-conformal technique is appropriate to deliver the whole dose to a limited volume. In UK, an intraoperative technique using a miniature beam of low energy of x-ray (50 Kv) has been developed (Targit). Milan's team have developed an intraoperative electrons beam radiotherapy using a dedicated linear accelerator in the operative room. In USA and Canada the MammoSite has been advised for clinical use in per-operative brachytherapy of the breast. These two last techniques are currently compared in phase III randomised studies to the standard whole breast irradiation followed by a tumour bed booster dose. In this review we will focus on the MammoSite technique and will describe the per-operative implantation procedure, radiological controls ad dosimetric aspects.

Thyroid stimulating hormone and selenium supply interact to regulate selenoenzyme gene expression in thyroid cells (FRTL-5) in culture.

In the absence of a sodium selenite supplement, FRTL-5 cells showed a reduced activity of cytosolic glutathione peroxidase (cGSH-Px), a marker of selenium status, indicating the cells were Se-deficient. Se-deficient cells showed a 65% reduction in cGSH-Px mRNA abundance but little change in abundance of either phospholipid hydroperoxide glutathione peroxidase or type 1 deiodinase (IDI) mRNA. In Se-replete cells increased thyroid stimulating hormone (TSH) caused a small decrease in IDI abundance but in Se-deficient cells TSH caused a large increase. The results indicate an interaction between TSH and Se status in the regulation of thyroid selenoenzyme synthesis.

Approximate Solution for the Spreading of a Droplet on a Smooth Solid Surface.

The same approach used by Boender, Chesters, and van der Zanden in the context of an advancing liquid-gas meniscus in a capillary tube is extended to the case of spontaneous spreading of a droplet on an ideal solid surface. The result is an ordinary differential equation for the droplet profile which can be solved if the meniscus inclination phi0 is specified at some distance lambda from the solid. As in the capillary-tube case, good agreement is obtained with experimental data obtained by the authors and by others if phi0 is set equal to the static contact angle (zero in cases investigated experimentally), taking lambda of the order of a molecular dimension (1 nm). A comparison of predicted dynamic contact angles in the spreading-drop and capillary-tube cases for given values of the capillary number indicates only a weak dependence of the behavior on the system geometry. De Gennes and co-workers have predicted that during the final stages of spreading the inner length scale lambda should be determined by the effects of disjoining pressure in the thin film adjacent to the contact line rather than by molecular dimensions. The lambda value implied by their model is derived, thereby establishing the regime of spreading in which such effects should be dominant. The observed behavior in this regime is found to correspond somewhat better with a lambda value of the order of a molecular dimension, although the differences are small. Although the explanation probably lies in the nonideality of even the smoothest surfaces, this result suggests that the simplest model, based on a single lambda value of the order of 1 nm, should provide an excellent predictive tool. Copyright 1998 Academic Press.