6), the failure

6), the failure see more of Coa_NP2 to relax aortic rings precontracted with 80 mM potassium suggested a possible role for voltage-dependent ion channels that may include potassium channels; however, the primary mediator could be calcium influx, which activates a calcium-activated potassium

channel and/or NO release [13]. Supporting this affirmation, the potassium-channel blocker, tetraethylammonium has been found to reduce the BNP-induced dilatation of brachial humans arteries [36]. As such, our findings demonstrate that the hypotension and vasodilatation caused by Coa_NP2 is consistent with the hypothesis that both NPR-B pathways activate and stimulate NO production in parallel. In conclusion, we isolated and characterized a new NP-like peptide from C. o. abyssus venom (Coa_NP2), and we also report a dose-dependent hypotensive effect of this peptide in association with increased nitrite production, as well as vasodilatory endothelium-dependent effects. Therefore, these data suggest that the NO-release dependent vasodilator action of Coa_NP2 may occur by stimulation of potassium channels. The authors report no conflicts of interest in this work. We would like to thank CAPES, CNPq, FAPEMIG and FAPESP (Brazilian agencies)

for financial support. “
“The authors regret for the error in Peptides 33 (2012), p. 207, Section 2.4. using the Triple TOF 5600 TOF MS Analyzer (Applied Biosystems)”

is corrected into “using the Triple ToF 5600 (AB Sciex). The authors selleck screening library would like to apologise for any inconvenience caused. “
“Collagens are characterized by the triple-helical structure resulting from the presence of repeating GXX’ triplets, where G is glycine, X is commonly proline (P), and X′ is commonly hydroxyproline (O). The fibrillar collagens I and II, whose Docetaxel ic50 main triple-helical domains comprise 338 such triplets, are the fundamental scaffolds of the extracellular matrix in bone, tendon (type I), and cartilage (type II) [4] and [7]. In blood vessel walls and skin, collagen I is interlaced with collagen III, having a 343-triplet helix, whereas non-fibrillar collagen IV networks form basal laminae in structures such as kidney glomeruli, lung alveoli, and blood vessel walls [19]. These collagens, along with the 24 other known collagen types, are widely distributed. Accordingly, a large repertoire of proteins bind to the collagens, including structural components of the extracellular matrix as well as cell receptors that mediate physiological processes such as cell migration, hemostasis, and wound healing. In 1995, Barnes developed a platelet-reactive model peptide, a GPO polymer now called collagen-related peptide (CRP) [18] which proved to bind the immune receptors, platelet Glycoprotein VI (GpVI) [10] and [29] and leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) [14].

3% and 36 6% (for gefitinib) and 10 9% and 31 0% (for vinorelbine

3% and 36.6% (for gefitinib) and 10.9% and 31.0% (for vinorelbine),

selleck inhibitor respectively. There was no statistical difference between gefitinib and vinorelbine in efficacy in chemotherapy naıve, unselected elderly patients with advanced NSCLC, but there was better tolerability with gefitinib [23]. Iressa Pan-Asia Study (IPASS) trial was conducted recently as a phase 3, randomly assigned previously untreated patients in East Asia who had advanced lung adenocarcinoma and who were nonsmokers or former light smokers to receive gefitinib (250 mg per day) (609 patients) or carboplatin plus palitaxel (608 patients). The primary end point was progression-free survival. The 12-month rates of progression-free survival were 24.9% with gefitinib and 6.7% with carboplatin–paclitaxel. In the subgroup of 261 patients ABT-199 in vitro who were positive for the epidermal growth factor or receptor gene (EGFR) mutation (96% have Exon 19 deletion or Exon 21 L858R mutation), progression-free survival was significantly longer among those who received gefitinib than among those who received carboplatin–paclitaxel (hazard ratio for progression or death, 0.48; 95% CI: 0.36–0.64; p < 0.001), whereas in the subgroup of 176 patients who were negative for the mutation, progression-free survival was significantly

longer among those who received carboplatin–paclitaxel (hazard ratio for progression or death with gefitinib, 2.85; 95% CI: 2.05–3.98; p < 0.001) [24]. Erlotinib in combination with chemotherapy as first-line treatment of NSCLC Pregnenolone has been evaluated in two large multicenter, randomized, placebo-controlled clinical trials. Two platinum-based doublets (carboplatin plus paclitaxel or cisplatin plus gemcitabine) were evaluated in combination with erlotinib versus placebo in the Tarceva Responses in Conjunction with Paclitaxel and Carboplatin (TRIBUTE) and Tarceva Lung Cancer Investigation (TALENT) trials, respectively. In the TRIBUTE study, 1000 patients with untreated advanced

stage IIIB/IV NSCLC were enrolled. The median over-all survival time (OS) for patients treated with erlotinib was 10.6 months, versus 10.5 months for the placebo group, the over-all response (OR) rates were similar in the erlotinib and placebo arms (21.5% vs 19.3%, respectively) [25]. In the TALENT trial, likewise, there was no statistically significant difference in any outcome, with a median OS of 301 versus 309 days, respectively. Therefore, there was no clinical benefit in either trial, and currently concurrent use of erlotinib with chemotherapy is not recommended in the first-line treatment of NSCLC unless the tumor has EGFR mutation [26]. Optimal trial was phase III randomized trial conducted recently in China assigned previously untreated 154 patients with known EGFR mutations (Exon 19 deletion or Exon 21 L858R mutation) and measurable disease to receive erlotinib or gemcitabine plus carboplatin. Progression-free survival was significantly improved with erlotinib (13.1 vs 4.6 months, HR 0.

For instance, because of untreated pulp mill discharges in the la

For instance, because of untreated pulp mill discharges in the late 19th and early 20th centuries, there were embayments on the west coast of North America where nothing lived, dead fish washed up daily, and there was no need to remove barnacles from the bottom of boats – there were no barnacles (Dexter et al., 1985). But nowadays municipal and industrial

effluent discharges, at least in North America and other developed countries, do not result in “dead areas”. The concern is for potential chronic rather than acute effects, and concerns are sometimes based on perceptions selleckchem rather than facts. Treatment is expensive in monetary terms (and, as noted above, can also be expensive in environmental terms). There are cases where treatment is necessary, but there are also cases where treatment may not be necessary and the monies used for treatment could be put to better use to improve human health (e.g., applying those monies to the health care system) and the environment (e.g., attempting to deal with arguably our greatest-ever environmental challenge: global warming). The third response is a variation on the second, invoking the Precautionary Principle (PP). Unfortunately the PP is too often misunderstood

or misrepresented; it is too often invoked to further human political or activist agendas, with LGK-974 chemical structure no understanding of its original meaning. The PP was originally developed in the 1970s as a concept within environmental science in Germany, a general rule of public policy-making

(EEA 2001). Specifically, the original and, I believe, most relevant PP stated that where there are potentially serious or irreversible threats to human health or the environment (or both) there is a need to reduce potential risks before there is strong proof of harm, taking account of the likely costs and benefits of action and inaction. Two subsequent different and, I believe, deficient definitions of the PP bear mention (for more details on these and other definitions, see EEA (2001) and SNIFFER (2005)). The United Nations Environment Program 1992 Rio Declaration 15 definition of Methane monooxygenase the PP failed to mention the cost-benefits of action and inaction: “Where there are threats of serious or irreversible damage, lack of full scientific certainty should not be used as a reason for postponing cost-effective measures to prevent environmental degradation”. The Wingspread Declaration (named after the Wingspread Conference Center, Racine, WI, USA) of January 1998, with 32 authors, focused on endocrine disrupting chemicals and stated: “Where an activity raises threats of harm to the environment or human health, precautionary measures should be taken even if some cause and effect relationships are not fully established scientifically.” This definition omitted not only the cost-benefits of action and inaction but also the important term ‘serious or irreversible damage’. A threat of harm may or may not materialize (i.e.

Despite the recent decrease in total catch compared with 10 years

Despite the recent decrease in total catch compared with 10 years ago, fish exports have increased constantly; this

increase seems to occur at the expense of local consumption and has caused significant increases in fish prices in local markets [44]. Artisanal fishing accounts for well over 90% of the total production [27]. The key fisheries resources, shown in Table 1, include pelagic fishery for tuna and tuna-like species and demersal fishery for fish, cuttlefish, shrimp, and lobster. Tuna and tuna-like species and cuttlefish are prevalent in the Gulf of Aden and the Arabian Sea, whereas demersal fish are more abundant in the Red Sea. Key pelagic species include yellowfin tuna, longtail tuna, little tuna, narrow-barred Spanish mackerel, Indian mackerel, anchovy, and sharks; key demersal fish species include emperors, groupers, snappers, and jacks [27] and [32]. Despite Sunitinib the lack of comprehensive selleck kinase inhibitor stock assessment studies and reliable catch statistics, it is believed that most fish stocks, except small pelagic species for which there is no market demand, are either fully exploited or overexploited [37]; interviews with fishermen and

different stakeholders confirm these beliefs. Cuttlefish (Sepia pharaonis) has been harvested since 1967 by industrial fleets in the Gulf of Aden and the Arabian Sea region. The intensive trawling on their spawning aggregations has led to overfishing and a major decline of the fishery by 1982–1983 with reported annual landings falling from around 9000 to 1500 t. Landings of the rock lobster (Panulirus homarus) virtually collapsed to near zero in the late 1990s from peaks of around 400 t in the early part of the decade. This collapse was attributed to the widespread use of nets rather than traps to capture lobsters [37]. Large-scale harvest of sea cucumbers started in 2003 with the advent of air compressors, which facilitated diving; this process

led, a few years later, to the collapse of the fishery [45]. Many important demersal fish stocks and some pelagic species, such as Indian Vasopressin Receptor mackerel [41], narrow-barred Spanish mackerel, and sharks [40] and [46], have experienced severe overfishing and their production levels have been beyond the maximum sustainable yields. The lack of FMPs, widespread IUU fishing, uncontrolled growth of fishing effort, and weak compliance and enforcement arrangements have led to significant economic losses associated with the suboptimal use of the resources, which has in turn resulted from weak and ineffective governance and subsequent overfishing. Small-scale fishermen typically use two types of fishing boats: small fiberglass boats called huris, 7–16 m long, with outboard engines and 2–6 crew members, and larger wooden boats called sambuks, 10–20 m long, with inboard or outboard engines and with a crew from 10 up to 25 or more [4] and [27]. Huris were traditionally used for single day trips in inshore waters, within 40 km of the shore [4].

That these fundamental observations clustered in a specific

That these fundamental observations clustered in a specific Selleckchem CYC202 stretch of time, on the other hand, is also intriguing. In the same, specific time interval,

another major change in scientific trends arose. The idea of a hematopoietic stem cell, a common multipotent progenitor for all blood cells, had been formulated long before (reviewed in [12]), but had remained dormant without attracting interest and above all, experimental effort. The idea exited the realm of theoretical postulates in 1961, with the seminal work of Till and McCulloch [13] and [14], admittedly the first experimental evidence for a common multipotent progenitor of blood cells. In essence, the fundamental discoveries of a dual system of stem cells in bone were not only almost synchronous, selleck chemicals llc but also arose from efforts across the iron curtain that fell at the end of WWII, and are the direct result of the way WWII ended. It was the attempt to develop strategies for radioprotection that gave a new impetus to the science behind what was to become stem cell biology. Not casually, the front page of the famous New England Journal of Medicine paper by E. Donnall Thomas reporting in 1957 [15] the first attempt of bone marrow transplantation in humans both recounts the lethal effects of nuclear warfare, and acknowledges the support of the Atomic Energy Commission of the USA.

Much more in bone science and science at large emanate from the same cradle: the biology of bone matrix [16] and [17] and the role of parathyroid glands [18], for example, and key techniques such as microradiography and autoradiography [16], [17], [19], [20] and [21], to name a few. At about the same time that something “osteogenic” was being discovered in bone marrow by Tavassoli and Crosby Tenoxicam [3], and by Friedenstein and coworkers [2], it was exactly autoradiography that made it possible to trace the kinetics of bone cells in vivo,

in a series of seminal studies by Owen and Macpherson [22], [23], [24] and [25]. This is how we learned about precursor cells of osteoblasts in the inner layer of the periosteum, about the origin of osteocytes from osteoblasts, and about the kinetics thereof. Not casually, the two independent lines of thinking about the origin and precursors of bone cells were to merge soon thereafter in the work of Owen, just like her background in physics and attention to biology had merged in her early work as a reflection of the post-war climate and strategic priorities. Even the work of Friedenstein (Fig. 1) and that of Owen (Fig. 2) united at one point [26], which was crucial to disseminate the significance of Friedenstein’s work in the West. That unification was also crucial to formulate the concept not only of a stem cell for bone, but also for different tissues together comprising the skeleton being connected to one another at the level of a common ancestor, rather than as separate entities as thought previously.

A third opportunity for research that could build on the results

A third opportunity for research that could build on the results reported here would be the in-situ investigation of ‘hot spot’ areas, past and contemporary, to characterize the substrate, water depth, slope, acoustic environment and oceanographic features in such areas, building on preliminary work done in 1977 (Fraker, learn more 1977). Sampling

of the bottom substrate in one of the Kugmallit Bay ‘hot spots’ was initiated in July 2013 and July 2014 (Hansen-Craik et al., 2013; D. Whalen, NRCan, unpubl. data), and results will be forthcoming. One requirement of the TNMPA management framework is to prohibit specific activities, or classes of activities, that could potentially negatively impact beluga or any part of the ecosystem in the areas upon which they depend (Canada, 2013 and Beaufort Sea Partnership, 2014). Given renewed and considerable interest by the petroleum industry in the Mackenzie Estuary (AANDC, 2012), the types of activities that may arise for screening include proposed flight corridors, ship GW-572016 solubility dmso traffic, seismic surveying, exploratory drilling, and various activities associated with the production of hydrocarbons. Other activities which might be proposed for the TNMPA include whale watching, gravel removal or dredging, by government

or local operators. Determining if any such activity would cause impacts on beluga, as required under the TNMPA regulations, would be impossible without detailed knowledge of the ways that belugas use their TNMPA habitats,

both in time and space. The mapped results presented here would be useful to decision makers and to proponents, at three stages: in initial screening of such projects, the detailed assessments which follow, and in the case of projects which are allowed, the setting of terms PLEK2 and conditions to mitigate potential impacts. This could take the form of ensuring key habitats (e.g., ‘hot spots’) and/or times of year are avoided, and that conservation efforts are targeted towards the most important areas and times (Williams et al., 2014). Hypothetically speaking, dredging of a new harbour or removal of gravel could have direct but localized effects on beluga habitats, compromising habits which concentrate prey or facilitate rubbing to slough skin (Smith et al., 1992), regardless of time of year. However, the spatial extent of disturbed habitat from such activities would be relatively localized, compared with, for example, anthropogenic activities which introduce underwater noise and the potential to disturb marine mammals (Erbe and Farmer, 2000; Lesage et al., 1999; Tyack, 2008 and Gervais et al., 2012. In those cases, there is potential for ensonification of an entire subarea, although only temporarily.

GSEA was performed for all treatment groups vs controls at same

GSEA was performed for all treatment groups vs. controls at same time point. Gene sets with a p value < 0.05 and an FDR value < 0.25 were considered being significantly regulated. Up- and downregulation of significant gene sets were visualized with heap maps. The p values were converted into Z values to enable clustering. Gene sets obtained positive or negative Z values when up- or downregulated, respectively. Hierarchical clustering was done as described above. For GSEA, five collections of gene sets were used: 1. Cell cycle: data taken from supplemental data of Whitfield et al., 2002 and Bar-Joseph et al., 2008. In these studies, cells were first synchronized at the

G0 cell stage and then stimulated to retain the cell cycle. Microarray analysis Bafilomycin A1 manufacturer was performed to detect genes

upregulated during certain cell cycle stages. Up- or downregulation of these gene sets is indicative for a higher or lower proliferation rate. Molecular concepts analysis enables to visualize networks in which the overlap between gene sets based on co-occurrence of genes are CYC202 clinical trial shown (Rhodes et al., 2007). This overlap was calculated based on the genes that were responsible for a gene set to be significantly affected. For this, either the top 20% of the genes being upregulated or the top 20% of the genes being downregulated was used. Gene set selection for molecular concepts mapping was more stringent than used for making heat maps. Gene sets were selected on a p value < 0.01 in combination with an FDR value < 0.25 according to GSEA statistics. In addition, gene sets containing ≤ 8 genes were excluded from the analysis. After applying these criteria, 74 upregulated and 80 downregulated gene sets remained. The significance of overlap between the gene sets was calculated based on the

binomial distribution using Venn-Mapper ( Smid et al., 2003). Gene sets showing significant overlap (Z value > 2.72 that is equal to p < 0.0001) were connected in a network that was visualized using Cytoscape ( Shannon et al., 2003). Genes from Sinomenine the gene sets with high overlap (high Z values) were clustered close to each other. Gene sets within a same cluster are expected to have a similarity in biological effects. These gene sets were merged, and heat maps showing the effects of all treatments on the genes of those merged gene sets were generated using GSEA. Seven-week-old male C57BL/6 mice were obtained from the breeding colony of Wageningen University and sacrificed by CO2 without any preceding treatment. The protocol was approved by the ethical committee for animal experiments at Wageningen University. The thymus was excised aseptically and collected in 3 ml RPMI 1640 medium, containing HEPES (Invitrogen Life Science, Breda, The Netherlands) with 10% heat-inactivated Fetal Bovine Serum (FBS) (Invitrogen Life Science), 100 U/ml Penicillin, and 100 μg/ml streptomycin (Invitrogen Life Science) (standard medium).

stigmurus as the main cause of scorpionism within the region ( Li

stigmurus as the main cause of scorpionism within the region ( Lira-da-Silva et al., 2000). However, due to the lack of information, the actual epidemiological impact of these incidents of scorpionism within these localities remains relatively obscure. Unlike the species mentioned above, T. bahiensis exhibits crossbreeding, which requires encounters between males and females during certain periods of the year. This scorpion can be found in the states of São Paulo, Minas Gerais, Goiás, Mato Grosso do Sul, Paraná, DAPT chemical structure Rio Grande do Sul and Santa Catarina ( Porto et al.,

2010). Scorpion venom is a complex mixture of components that can be separated into an insoluble, generally non-toxic, fraction and a soluble fraction containing toxic peptides that exhibit activity on ion channels, in addition to mucopolysaccharides, nucleotides, vasoactive amines (serotonin or histamine), protease inhibitors and enzymes (Gazarian et al., 2005; Rodríguez de la Vega et al., 2010). In general, it is believed that the toxic activity of scorpion venom is predominantly attributed to the presence of peptides that disrupt Na+, K+, Ca+ and Cl− channels

in neuronal cells (Possani et al., 2000). Recent studies have shown that apart from these peptides, several molecules PI3K inhibitor that play a role in scorpion poisoning or that exhibit properties of biotechnological interest are also present in scorpion venoms (Wu et al., 2010; Zeng et al., 2012; Zhao et al., 2011). The specific treatment for Tityus envenomation is the intravenous administration of heterologous antivenoms. Recently, a double-blind study

evaluating the effectiveness of the serum therapy in the treatment of children who were stung by scorpions and admitted to intensive care units showed that the specific F(ab’)2 antivenom is extremely effective most in reversing the symptoms of poisoning, reducing the use of sedation and of circulating levels of venom ( Boyer et al., 2009). In contrast, other studies have found no significant benefit in the administration of antivenom to patients stung by scorpions ( Abroug et al., 1999). There is evidence that the antivenom is ineffective in the treatment of severe cardiovascular manifestations due to the involvement of the autonomic nervous system in the aetiology of these manifestations ( Amaral and Rezende, 2000). In Brazil, the following two therapeutic scorpion antivenoms are produced by the Butantan Institute: 1) an anti-arachnidic antivenom, which is obtained by the immunisation of horses with a mixture of venoms derived from T. serrulatus (57%), Phoneutria nigriventer (21.5%) and Loxosceles gaucho (21.5%), and 2) an anti-scorpionic antivenom, which is obtained by the immunisation of horses with a mixture of venoms derived from T. serrulatus (50%) and T. bahiensis (50%). Based on the potential diversity of composition and toxicity of Tityus spp.

Gauchan et al , 2009a, Gauchan et al , 2009b and Gauchan et al ,

Gauchan et al., 2009a, Gauchan et al., 2009b and Gauchan et al., 2009c showed that blocking TRPM8 function by administering capsazepine inhibits oxaliplatin-induced cold allodynia. Langerhans cells (LC) are skin’s resident immune cells and studies have shown an increase in its number in patients with CRPS-I and inflammatory immune diseases.

Siau et al. (2006) have demonstrated an increase in LC cells in skin in vincristine and paclitaxel evoked Adriamycin research buy painful neuropathy and linked the development of pain manifestation with increased LC cells. There are different mechanisms by which LC cells may contribute to pain development including release of NO (Qureshi et al., 1996), pro-inflammatory cytokines (Deng et al., 2003) and neurotrophic factors (Torii et al., 1997) that causes sensitization of remnant nociceptors leading to spontaneous discharge and mechano-hypersensitivity. Ledeboer et al. (2007) demonstrated that paclitaxel treatment-induced neuropathic pain is associated with induction of TNF-alpha and IL-1beta in the lumbar DRG. Furthermore in the same study,

administration of intrathecal IL-10 genes attenuated paclitaxel induced up-regulated pro-inflammatory cytokines along with decrease in mRNA expression of CD11b, a macrophage/dendritic cell marker, in the lumbar DRG. It suggests that macrophages (resident CD11b+ immune cells) are the potential sources of these pro-inflammatory cytokines that in-turn sensitize primary sensory afferents and modify sensory input to the spinal dorsal horn to facilitate pain. An important role of inflammatory mediators is described in our studies using vincristine-induced neuropathic model selleck inhibitor (Kaur et al., 2010 and Muthuraman and Singh, SPTLC1 2011). The experimental studies have shown that glial cell inhibitors such

as propentofylline, thalidomide and minocycline (selective for microglia) attenuate paclitaxel/vincristine induced neuropathic pain (Cata et al., 2006 and Sweitzer et al., 2006), supporting a role for activated (micro)glial cells in these conditions. It has been reported that macrophage accumulation and activation in the DRG of paclitaxel-treated rats contribute to generation and development of the neuropathy. Nishida and co-workers demonstrated an up-regulation of matrix metalloproteinase-3 (MMP-3, stromelysin-1) and CD163, a macrophage marker in the DRG. MMP-3 up-regulation occurs prior to macrophage accumulation suggesting that the up-regulation of MMP-3 followed by macrophage activation in the DRG may be a significant event to trigger a series of reactions developing paclitaxel-induced peripheral neuropathic pain (Nishida et al., 2008). A recent study has shown an increase in IL-6 which is correlated with appearance of bortezomib-induced neuropathic pain (Mangiacavalli et al., 2010). The studies have suggested the critical role of arachidonic acid derived mediators including prostaglandins i.e.

Correction factors were determined

Correction factors were determined LBH589 as described previously (Krais et al., 2011). CE-LIF analysis was performed on a PACE™ MDQ system with a Laser System Sapphire 488 CW (λem = 488 nm) from Coherent (Germany). Electrolyte and separation conditions were: 90 mM SDS in a solution of 90% (v/v) sodium phosphate buffer (18 mM, pH 9.0) and 10% (v/v) methanol as organic modifier; fused-silica capillary column, total length 59 cm; length to the detection window 48.5 cm; inner diameter 50 μm; injection 2.5 psis; temperature 20 °C; applied voltage 20 kV. Data were collected and analysed using 32 Karat software (version

5.0, Beckman Coulter). Time corrected individual peak areas were determined as described previously ( Krais et al., 2011). Mouse ES cells are increasingly being Everolimus chemical structure used in mechanism-based genotoxicity testing (Hendriks et

al., 2012 and Pines et al., 2011). They provide an attractive system as they are untransformed, continuously proliferating cells that are proficient in the main DNA damage signalling pathways and cell cycle control systems and are genetically stable (Hendriks et al., 2013). As most environmental carcinogens require metabolism to exert their genotoxic activity we compared ES cells and MEFs derived from mice on a C57Bl/6 genetic background carrying wild-type Trp53 for their ability to metabolically activate environmental carcinogens. We selected a variety of environmental check details carcinogens of different chemical classes

where the metabolism is well studied and characterised. The cell culture test conditions were based on previous studies using these carcinogens in mammalian cells ( Arlt et al., 2007, Hockley et al., 2008, Kucab et al., 2012 and Simoes et al., 2008). We used carcinogen-DNA adduct formation as a surrogate measure of the relevant XME activity as all tested environmental carcinogens induce specific and structurally-identified DNA adducts which can be detected by the 32P-postlabelling assay ( Schmeiser et al., 2013). The metabolic activation of BaP is catalysed predominantly by cytochrome P450-dependent monooxygenases (CYPs), mainly CYP1A1 and CYP1B1, in combination with microsomal epoxide hydrolase (mEH), resulting in the highly reactive BaP-7,8-dihydrodiol-9,10-epoxide (BPDE) capable of forming covalent DNA adducts (Fig. 1A) (Arlt et al., 2008, Stiborova et al., 2014a and Stiborova et al., 2014b). The effect of BaP on cell viability was similar in ES cells and MEFs at concentrations up to 5 μM (Fig. 2A and B). With a loss of viable cells of around 50% at 10 μM after 48 h of exposure, ES cells were more sensitive than MEFs. ES cells and MEFs were both capable of generating BaP-induced DNA adducts (Fig. 3A and B). The major DNA adduct (assigned spot B1) was previously identified as 10-(deoxyguanosin-N2-yl)-7,8,9-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene (dG-N2-BPDE) ( Arlt et al., 2008).