8% with 90.6% of patients reporting excellent/good cosmesis at 60 months [49] and [50]. A retrospective multi-institutional analysis of nearly 500 patients with 24-month followup demonstrated a 1.2% IBTR with more than 90% of patients having excellent/good cosmesis (48).

Although there are no published randomized comparisons of balloon APBI with WBI, a retrospective matched-pair Thiazovivin datasheet analysis comparing outcomes from the ASBS Registry with those of WBI patients from the SEER database found no difference in rates of RR or survival at 5 years (65). External beam RT has also been developed as a method to deliver APBI. Two older randomized trials from the United Kingdom found increased rates of LR with partial breast techniques that are inconsistent with today’s standard techniques [17] and [18]. A more recent prospective trial from Italy found reduced rates of acute

toxicities with intensity-modulated RT–based APBI (21). RTOG 0319 was a Phase I/II trial of 52 patients undergoing external beam RT APBI and found the 4-year rate of IBTR to 6%, with only 4% of patients developing Grade 3 toxicity. Although two recent series have documented increased rates of toxicity and poor cosmesis, an interim analysis of the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-39/RTOG 0413 trial evaluating the 1386 patients receiving three-dimensional conformal radiotherapy APBI found no significant toxicity issues at 41 months with a 3% rate of Grade 3 or more fibrosis [52], [53] and [66]. On the contrary, recent analysis of the Randomized find more Trial of Accelerated Partial Breast Irradiation Trial comparing external beam APBI and WBI found that this form of APBI was associated with an increased rate of adverse cosmesis and Grade ½ toxicities with short-term followup (67). Intraoperative therapy, although included in Table 2 as a partial breast technique, should not be grouped

with other APBI modalities in terms of outcomes, toxicities, and guidelines recommendations because of significant differences in the technique. Although initial outcomes from a randomized noninferiority trial comparing intraoperative radiation therapy (IORT) with WBI found no difference in outcomes at 4 years, a more recent update suggested a 2% higher rate O-methylated flavonoid of IBTR compared with WBI, whereas updates from the Milan trial have found higher than the expected rates of IBTR [20], [68] and [69]. Patient evaluation for APBI should be a multi-disciplinary approach that incorporates the breast surgeon, radiation oncologist, and medical oncologist. Ideally, the patient should be evaluated by a radiation oncologist before or within a few days of surgery. A detailed history should be performed to rule out absolute/relative contraindications for BCT in general or APBI including pregnancy, prior RT to the breast or chest, connective tissue disease, or strong family history (potentially requiring genetic testing).

The WGA binding to the altered cell surface glycans was highly specific and aided click here in the discovery of lesions that would have been missed during conventional endoscopy [22]. The results presented by Bird-Leiberman et al. are very similar to the data shown in this study, which confirms the use of lectin molecules as potential markers of neoplasia in lesions that cannot be visualized clinically in white light. Moreover, this approach can be used to determine surgical boundaries in the oral

cavity prior to tumor resection. One of the limitations of the study has been the usage of the permeation chemical DMSO. Although FDA approved for some applications, it does have some minor side effects including skin rash, nausea, and headache [37] and [38]. Another limitation is that tissue samples were incubated with the WGA-fluorophore solution

for 1 hour which would not be clinically feasible. selleck inhibitor These and other limitations will be addressed through additional studies to determine the most adequate composition of AF350-WGA solution for clinically relevant cancer detection. This study investigated the efficacy of fluorescence imaging using topically applied lectin-fluorophore conjugates as compared to conventional tissue autofluorescence in distinguishing tumor tissue. The results revealed that the changes in glycosylation could differentiate normal from cancerous tissues in the oral cavity with high SNRs. Therefore, this technique Oxymatrine seems promising as a non-invasive screening method for premalignant and malignant mucosal tumors, and as a method for defining surgical margins and monitoring cellular changes over time. Provided technologies that target cancer on a molecular level, clinicians could effectively recognize lesions in earlier stages, thereby enabling early detection and treatment. To further evaluate this approach for oral cancer screening, in vivo testing

with a larger sample size needs to be performed to obtain sensitivity and specificity values. Nevertheless, to the best of our knowledge, the authors have, for the first time, demonstrated that topical application of lectin probes to mucosal epithelial tissues followed by molecular imaging of the tissues can be used to spatially differentiate cancerous and normal tissue of the oral cavity. “
“Angiogenesis is essential for tumor growth and progression [1]. Antiangiogenic therapies have been demonstrated effective on the suppression of tumor growth [2]. Paradoxically, antiangiogenic strategies can also induce local and distant metastasis [3]. Reduced oxygen supply leads to the stabilization and activation of the transcription factor hypoxia-induced factor 1 (HIF-1) [4]. Hypoxia and the expression of HIF-1 are correlated with cancer metastasis and unfavorable prognosis [5]. Through activation of the Twist, hypoxia induces epithelial-to-mesenchymal transition [6], which was associated with cancer metastasis [7].

Eight isolates had three codon changes (8/56: 14%), and twenty-one isolates had two codon Nintedanib chemical structure changes (21/56: 38%) (Table 1). The isolates with multiple codon changes generally included changes at codon 533 (26/30: 87%). The remaining isolates (26) had only one codon change (26/56: 46%), most commonly at codon 531 (22/26: 85%) (Table 1). Changes to codons 531 and 533 occurred in 53 patients (53/56: 95%). The mutation S531 L (TCG/TTG) was by far the most frequent (35 patients: 35/56: 63%), followed by L533R (CTG/CGT) (12 patients: 12/56: 21%), L533P (CTG/CCG) (7 patients: 7/56: 13%), L533R

(CTG/CGG) (5 patients: 5/56: 9%) and H526D (CAC/GAC) (4 patients: 4/56: 7%) (Table 2). Based on the information provided by the TB drug resistance mutation database [23], which lists all published mutations that have been associated with rifampicin resistance, 15 of the 30 different missense codon changes obtained (excluding silent codon changes) represent novel codon changes (50%). Most of the novel SB203580 price changes were located in codon 533. Novel codon changes represent 31 of the total 92 codon changes (34%) and were identified in 30 of the 56 patients (54%) (Table 2). The new codon changes at positions 529 and 532 indicate mutations at new locations. The codon changes included (43) different base pair changes (nucleotide position or base) resulting in a total of 134 bp changes (63 transitions and 71 transversions).

Of the 97 codon changes, 68 (70%) included a single base pair change, 22 (23%) included two, and 7 (7%) included three base pair changes. It appears that 18 codon changes involved 2 bp inversions (Table 1). Most of the missense codon changes represented

learn more non-conservative amino acid replacements. The most frequent codon changes at position 531 involve a switch from a polar to a hydrophobic residue (S/L, I), while the changes at position 533 resulted in a switch from a hydrophobic to a charged residue (L/R). Several of the codon changes involved mutations to proline, a known secondary structure disrupter (Table 2). The fact that all isolates with phenotypic resistance to rifampicin used in this study exhibited amino acid changes in the RRDR region demonstrates the importance of the RRDR hotspot region in the resistance of clinical TB isolates in Syria. Several studies have indicated that this region is responsible for 90–95% of RIF-resistance cases [24]. However, many new mutations were identified in this study, and some were found at new locations within the RRDR. Notably, the vast majority of patients (95%) had mutations in codons 531 and/or 533. This could greatly reduce the expense and complexity of future early detection efforts in the local patient pool. Earlier studies [24] have asserted the importance of codon positions 526 and 531 to the observed resistance. This is true also in neighboring countries, such as Turkey.

Tumor growth was measured using caliper daily, and tumor volume was calculated according to the formula: volume = length × width2 × 0.5. The human B-cell lymphoma-extra large (Bcl-xL) and myeloid cell leukemia-1 (Mcl-1) 3′UTR luciferase reporter constructs and these constructs with miR-133a target site deletion

were made as we described previously [15]. All constructs were confirmed by DNA sequencing. Luciferase reporter assay was performed as reported [15]. Briefly, at 36 h post transfection, luciferase activities were detected using Dual-Luciferase Reporter Assay System (Promega) following the manufacturer’s instructions. Data were normalized by Bcl-2 inhibition dividing Firefly luciferase activity with that of Renilla luciferase. Cells and grinded human tissues were lysed using M-PER Protein Extraction Reagent (Pierce) supplemented with protease inhibitor cocktail (Calbiochem). Protein concentrations of the extracts were measured with BCA assay (Pierce) and equalized with the extraction reagent. Equal amounts of the extracts were loaded and subjected to SDS-PAGE, transferred onto nitrocellulose membranes, and then blotted as reported [15]. Antibodies specific to Bcl-xL, Mcl-1, β-actin, and horseradish peroxidase-coupled secondary antibodies were purchased from Cell Signaling

Technology. Densitometric analysis was done with Labworks Image Acquisition and Analysis Software (UVP, Upland, CA). The background was subtracted, and the signals of the detected bands were normalized to the amount of loading control β-actin band. Data are shown as mean ± s.d. Statistical comparisons between groups were analyzed

selleck chemicals using Student’s t-test and a two-tailed p < 0.05 was considered to indicate statistical significance. The correlation between miR-133a expression and clinical osteosarcoma stages was analyzed using Spearman's rank correlation coefficient assay in SPSS 17.0. Analysis of overall survival in osteosarcoma patients was performed using log-rank test in SPSS 17.0. The correlation between miR-133a expression and Bcl-xL or Mcl-1 protein levels was analyzed using Pearson's correlation coefficient assay in SPSS 17.0. In order to investigate the roles of miR-133a in human osteosarcoma development, we compared miR-133a expression in human normal osteoblastic cell line hFOB 1.19 with that Liothyronine Sodium in human osteosarcoma cell lines MG63 and U2OS by real-time qRT-PCR. And miR-133a expression was significantly decreased in osteosarcoma MG63 and U2OS cells (Fig. 1A). Furthermore, in the 92 pairs of human primary osteosarcoma tumor and adjacent normal tissue samples, miR-133a expression was significantly suppressed in tumor tissues as compared to that in adjacent normal tissues (Fig. 1B). These results suggest that miR-133a is downregulated in osteosarcoma cells, which might be involved in human osteosarcoma development. We next investigated whether the downregulation of miR-133a was correlated with osteosarcoma progression.

Patients were shown the 20 pairs of chimeric face

tasks in turn and asked to indicate verbally for each display whether the upper or lower member of each pair looked happier, just as in Mattingley et al., 1993 and Ferber et al., 2003 and Sarri et al. (2006). The stimuli were placed in front of the patients on a table, centred on the mid-sagittal plane of their head and trunk, and remained in view until the patients gave a response, without any time limit. For the gradients task, 20 pairs of greyscale gradients were constructed analogously to those in Mattingley et al. (1994). 10 pairs of greyscale gradient rectangles, consisting of a continuous scale of grey shades varying from absolute white at one end to absolute black at the Docetaxel cost other end were produced and printed on A4 sheets of paper. Each pair consisted of two rectangles, one being the mirror-reversed image of the other, one presented above and one below (see Fig. 3C). Each rectangle was bound by a .5 mm black outline.

The two rectangular strips varied in length from 10–20 cm (thus subtending approximately 15–28°), in increments of 1.5 cm and were kept at a constant height of 5 cm (approximately 4°). The two strips were always kept apart at a constant vertical separation of 2 cm. These 10 pairs were then mirror reversed to produce another 10 pairs. Patients were presented with all 20 pairs of identical but mirror-reversed greyscale gradient rectangles and asked to report verbally Atorvastatin whether the upper

or lower member of each pair looked darker (by saying ‘top’ or ‘bottom’), as in selleck inhibitor Mattingley et al. (1994). The stimuli were placed in front of the patients on a table, centred on the mid-sagittal plane of their head and trunk and remained in view until the patients gave a response, without any time limit. For the explicit chimeric/non-chimeric face discrimination task, 20 non-chimeric (‘real’) and 20 chimeric face stimuli were used, taken and adapted from Mattingley et al. (1993). The chimeric face stimuli were constructed from half-parts of the 20 non-chimeric face stimuli. The construction of the chimeric face stimuli was identical to the one described for the chimeric face lateral preference task. Each face stimulus subtended approximately 12° × 16° and unlike the emotional judgement task, where faces were presented in pairs, each face here was now presented individually. See Fig. 3B for an example of a non-chimeric and a matched chimeric face stimulus (note that this illustration depicts two potential successive trials, although in practice the face on one trial was unlikely to relate to that on the next). All 20 chimeric face stimuli were intermingled with the 20 non-chimeric face stimuli, so a total of 40 individual face stimuli were presented in random sequence. Each stimulus was presented briefly in the centre of a computer monitor for approximately 2.

The measured S/Vp represents an average of water confined within the triple and two grain junctions. In the long displacement time, Δ ≫ lp2/Do, D (Δ)/Do asymptotes to 1/α, where α is geometric tortuosity. Tortuosity is the ratio of the path length a molecule travels in a porous media to the geometric length traversed

α = lpath/lgeom and is a measure of inter-connectivity of the pore space [28]. Here we are limited to observing the approach to asymptotic diffusion, out to Δ ∼ 1000 ms due to NMR signal loss via T1 magnetic relaxation , and therefore measure an effective α. Fig. 3 shows displacement time dependent diffusion evolution with ice aging for the ice control lacking protein, ice with ECP, ice with rIBP(2) and ice with rIBP(4). The short time slope of the Ganetespib solubility dmso D (Δ)/Do curve for the ice control yields an effective diffusion distance lp that increases from 2.5 ± 0.1 μm at t = 25 h to 4.2 ± 0.1 μm at 790 h, consistent with ice crystal growth and subsequent larger elongated liquid veins (lp = dvein/4) and planar junction thicknesses (lp = dplane). AZD5363 D (Δ)/Do of the ice control at t = 790 h approaches a larger asymptotic value, or smaller effective tortuosity α. A Padé approximation can be used to interpolate between the short and long time [29] and [30], resulting in an estimation of tortuosity [29] and [31]. The Padé fit includes a fitting parameter θ with units of time that represents the time

for a particle to diffuse the distance needed to reach the tortuosity limit. For the ice control at t = 25 h, α is 4.2, while at t = 790 h it decreases to

3.7, consistent with ice crystal coarsening. Ice with BSA (not shown) exhibited similar behaviour to the Amino acid control sample that lacked protein. The D (Δ)/Do behaviour for the ice with rIBP(4) remained stationary over 1000 h. This lack of ice microstructural evolution is evidence of irreversible IBP binding [32], and the longevity of the effect indicates microbial activity is potentially a factor for consideration in ice rheology models where ice structure is a parameter. Ice with rIBP(4) also had the smallest effective diffusion length, lp = 1.0 ± 0.5 μm, and largest tortuosity, α = 47.0, at t = 819 h, therefore providing direct experimental evidence of smaller ice crystal structure and smaller liquid veins. Ice with rIBP(2) had lp = 1.5 ± 0.5 μm and α = 12.2 at long times (t = 810), while ice with ECP had lp = 3.0 ± 0.5 μm and α = 8.9 at long times (t = 933 h). This trend suggests that larger overall crystal sizes and diffusion lengths correlate with decreasing IBP concentration. The D (Δ)/Do data asymptotes to larger diffusion values (a smaller tortuosity) with decreased IBP concentration, again indicative of larger ice crystals and larger more elongated liquid veins. Despite microstructural differences due to IBP, water content measured from the liquid state 1H NMR signal [33] was stable between 2 and 2.

The images acquired with Cellomics™ Arrayscan® were analyzed by Spot Detector

V4 BioApplication. Neutral lipid accumulation: Cells were washed twice with HBSS (+Ca2+/Mg2+), stained with Hoechst 33,342 Ibrutinib in vivo and BODIPY® 493/503 (4,4-difluoro-1,3,5,7,8-pentamethyl-4-bora-3a,4a-diaza-s-indacene) (2 μM in DMSO) (Invitrogen, USA) and incubated 15 min at 37 °C. The images acquired with Cellomics™ Arrayscan® were analyzed by Compartmental Analysis V4 BioApplication. Phospholipids accumulation: Cells were washed twice with HBSS (+Ca2+/Mg2+) and stained HCS LipidTox™ Red (1:1000 in culture medium) (Invitrogen, USA) for 24 h at 37 °C in culture medium. After 24 h, the cells were washed 3 times with HBSS (+Ca2+/Mg2+), stained with Hoechst 33,342 and incubated 10 min at 37 °C. The images acquired with Cellomics™ Arrayscan® were analyzed by Spot Detector V4 BioApplication. FastLane Cell Multiplex Kit (200), (Qiagen, USA) was used to isolate first-strand cDNA directly from cultured cells without RNA purification according to manufacturer’s instructions. RT–PCR was performed using a StepOnePlus™ Instrument (Applied Biosystems, USA) Dasatinib in vivo in the presence of TaqMan® Gene E probes (Table 1) (Applied Biosystems, USA). Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was used as internal control. A volume of

20 μl was the used for each reaction. Relative gene expression was analyzed using the 2−ΔΔCt method. Statistical comparisons were performed between each dose group and the control using two-way ANOVA. Values were first normalized within each experiment in percent of control, to make the experiments comparable. The data were obtained from 3 independent experiments, each of them consisting

of 3 replicates. Statistical analysis was conducted using Graph Pad Prism 6 software. Differences compared to respective daily controls were considered as statistically ID-8 significant for *p < 0.05. Following isolation, primary rat hepatocytes were purified and cultured in Collagen I-coated plates. After the addition of a layer of Matrigel™, hepatocytes showed typical cuboidal morphology within the same day (Fig. 1A), whereas the canalicular networks were visible only after 2–3 days in culture (Fig. 1B). After 8 days in culture rat hepatocytes started to lose their cuboidal morphology and acquired spindle-like shape (Fig. 1C and D) together with dead cell detachment from the wells (Fig. 1E). In contrast, cells receiving a second layer of Matrigel™ on day 7 showed significant improvement of the culture quality. The cells maintained their morphology together with a lower disruption of the canalicular networks after 8 days (Fig. 1H–J).

BMD. The variation in Tt.Ar was most strongly predicted by age, height, and body mass (25%) and the addition of grip strength to the model accounted for an additional 19% of the variance in Tt.Ar. Age, height, and body mass

were the only significant predictors of Ct.Po accounting for 20% of the variance in this parameter. For the male cohort, sporting activity was the only significant predictor of Tt.BMD and Tb.BMD at the distal radius, accounting for 20% and 29% of the variance in these parameters, respectively. Conversely, age, height, and body selleck chemicals mass explained 54% of the variance in Ct.BMD, grip strength accounted for an additional 6.4% of the variance, and sporting activity had a negligible effect. Sporting activity was the only significant predictor of micro-architectural parameters, accounting for 26%, 22%, and 29% of the variance in Tb.N, Tb.Th, and Tb.Sp, respectively. For bone strength, age, height, and body mass accounted for 29% of the variance in failure load. The addition of grip strength to the model BTK assay had no effect, while sporting activity accounted for an additional 29% of the variance in failure load. For the female cohort, age, height, and body mass accounted for approximately 43%, 28%, and 16% of the variance in Tt.BMD, Ct.BMD, and Tb.BMD, respectively. Knee extension torque did not explain any of the variance in Ct.BMD, but did

explain 8% of the variance in Tt.BMD and 18% of the variance in Tb.BMD. Sporting activity was a predictor of Ct.BMD and Tb.BMD, accounting for approximately 13% of the variability in these parameters; however, sporting activity was not a significant predictor of Tt.BMD. Knee extension torque was the only predictor of Tb.Th, and accounted for 8% of the variance. Tb.Sp was only predicted by

sporting activity, explaining 13% of the variance. In terms of bone strength, age, height, and body mass explained 17% of the variance in failure load, knee extension torque explained 30% of the variance, and sporting activity accounted for 17% of the variance in failure load. For the male cohort, age, height, and body mass accounted for 23% of the variance in Tt.BMD, 59% of the variance in Tt.Ar, and 30% of the variance in failure load. Knee extension Baf-A1 in vitro torque was not a significant predictor of any HR-pQCT parameters at the distal tibia in the male cohort. Failure load was the only parameter predicted by sporting activity, which accounted for an additional 30% of the variance in bone strength. This study investigated the relationship between loading modalities present in three sporting activities and BMD, bone macro- and micro-architecture, and estimated bone strength through the use of three-dimensional imaging technology (HR-pQCT) and applied non-invasive mechanical testing techniques (FEA). Additionally, we investigated the relative contribution of age and body size, muscle strength, and sporting activity to HR-pQCT derived bone parameters.

Such precipitates can also affect the HTS resulting in poor liquid dispenses on the automation equipment. Tris buffer contains a free amine group which can react with enzymes and/or substrates, altering the equilibrium of the system. Tris is also able to chelate metal ions which could have

deleterious effects on the activity of enzymes requiring metals for catalysis or structure (Desmarais et al., 2002). There are many subtleties to consider when choosing a detection method for following an enzymatic FG-4592 nmr reaction in HTS, including throughput, sensitivity, cost and assay robustness, as well as the nature of the reaction under investigation and that of the products and/or substrates to be measured. No detection method is perfect – they are all utilized with some caveats – but for most enzyme classes, it is possible to strike a balance between these requirements to develop a useful assay. Many of the methods that are introduced here will be discussed with respect to specific enzyme classes and technologies later in this review. Directly monitoring a reaction as it is happening is referred to as a continuous read. Continuous reading typically requires a spectrophotometer/fluorometer capable of rapidly collecting data Trametinib in vivo from multiple time points and the ability of the

molecules being monitored to absorb or emit light in a reaction dependent way. Some examples of suitable systems used

in continuous detection are observing the change in either absorbance or fluorescence upon the interconversion of NAD and NADH, the production of fluorescent labels such as amino methyl coumarin (AMC) by proteolysis of AMC-labeled peptides, and the ability to observe changes in light scattering upon large protein complex formation. Continuous detection provides the advantage of observing an entire reaction time course G protein-coupled receptor kinase from a single mixture of substrate and enzyme, which minimizes the error in data by minimizing the need for multiple transfers and excess handling of the reaction components. However timing is a key variable that must be controlled particularly if a single time point is chosen for the assay as it can be difficult to stop a continuous reaction without disrupting the system or interfering with detection. In the specific case of fluorescence detection for enzyme assays one method to address “overriding” of the assay signal by compound fluorescence is to measure the reaction progress in a kinetic mode. Unless the reaction under study is slow, on the order of tens of minutes, only fast-scanning readers or whole-plate imagers (such as the PerkinElmer ViewLux™) allow for unbiased and speedy repeated measurements of microtiter plates. However, often a simple method where two-time points are collected allows one to estimate the reaction rate by simple subtraction of the two data points.

In accordance with a recent study ( Stiborova

et al., 2014b) we suggest that adduct spot B2 is a guanine adduct derived from reaction with 9-hydroxy-BaP-4,5-epoxide. Using CYP1A1 reconstituted systems it was recently shown that the formation of dG-N2-BPDE (adduct B1) depended on the presence of epoxide hydrolase while adduct B2 was solely http://www.selleckchem.com/products/Dasatinib.html formed when CYP1A1 and NADPH:cytochrome P450 oxidoreductase (POR) only were present ( Stiborova et al., 2014b). In MEFs two additional BaP-derived DNA adduct spots were detectable that were not structurally identified. No such adduct spots were detected in control (untreated) cells (data not shown). In ES cells BaP induced up to 126 ± 31 adducts per 108 nucleotides at 10 μM after 48 h, with adduct levels being ∼3-fold lower after 24 h ( Fig. 3A). BaP–DNA adduct levels in MEFs were manifoldly Rapamycin concentration higher ( Fig. 3B). The highest DNA adduct level in MEFs was observed at 2 μM after 48 h of BaP exposure (4583 ± 392 adducts per 108 nucleotides), which was 44 times higher than in ES cells under the same experimental conditions. In a recent study using primary HUFs treated with 1 μM BaP for 48 h, levels of 175 ± 62 adducts per 108 nucleotides were detected ( Kucab et al., 2012), indicating that the response of MEFs to BaP can differ. However, it may also be difficult to try to directly compare these findings as strain

differences (C57Bl/6 versus 129/Sv) and the p53 phenotype (Hupki versus Trp53) might have influenced the results between studies. Because cellular levels of p53 protein increase via post-transcriptional mechanisms upon genotoxic stress (Hockley et al., 2008), we measured protein expression of p53 and its downstream target p21 (Fig. 4). p53 and p21 expression was not altered in ES cells after BaP exposure (Fig. 4A), however, a clear increase in p53 expression was observed in BaP-treated MEFs while p21 remained unchanged (Fig.

4B). These results were in line with the results obtained by 32P-postlabelling analysis. ES cells have been shown to contain a higher amount of p53 than differentiated cells (Solozobova and Blattner, 2010) and regulation of p53 is known to differ in ES cells and differentiated cells, thus the p53 response to DNA damage enough in these cell types may also be different (Liu et al., 2014 and Solozobova et al., 2009). In order to determine whether the differences in BaP-induced DNA adduct levels observed between ES cells and MEFs could be due to differences in their metabolic competence, the expression of XMEs involved in BaP metabolism was evaluated. We therefore analysed Cyp1a1 and Nqo1 mRNA expression by RT-PCR. In BaP-treated ES cells expression of Cyp1a1 was up-regulated ∼40-fold ( Fig. 5A) independent of the BaP concentration used, which was in line with the observed BaP-induced DNA adduct levels. In MEFs BaP exposure resulted in a massive induction of Cyp1a1 expression ( Fig.