Now showing items 21-40 of 2673

    • Clinical investigation of flat pack toric contact lenses and wearer attitudes to environmental impact

      Ghorbani Mojarrad, Neema; Rountree, L.; Terry, L.; Bruce, Heather; Hallam, Emily; Jolly, Louise; Retallic, N.; Evans, K. (2023-11)
      Objectives: To investigate the performance of a novel flat pack toric daily disposable contact lens compared with traditionally packaged toric lenses in a randomized, crossover study. Environmental attitudes to contact lens wear were also explored. Methods: Habitual contact lens wearers were recruited to wear a hioxifilcon A (Miru 1 day Flat Pack Toric, Menicon, Nagoya, Japan) test lens and a control lens: either nelfilcon A (Dailies AquaComfort Plus, Alcon, Geneva, Switzerland) or etafilcon A (1-Day Acuvue Moist, Johnson & Johnson, New Brunswick, NJ). Objective lens performance was assessed at fitting, and participants wore lenses in a randomized order for three consecutive days. Subjective measures of lens performance (comfort, vision, and handling) were then assessed by a questionnaire, with further questions on overall lens preference and environmental perceptions. Results: Objective measures of lens fit were similar for the test and control lenses, except for distance VA which was better with the control lenses (P<0.05; difference of two logMAR letters). End of day comfort was greater with the test lens, but this did not reach significance. Both lenses demonstrated similar scores for overall satisfaction. 87.5% of participants indicated the environmental impact of contact lenses to be important/extremely important to them, with 100% of participants identifying the flat pack packaging as having a smaller environmental impact. Conclusion: Overall, the lenses used in the study performed to similar levels. Environmental credentials are important to contact lens wearers, which may contribute to overall lens preference.
    • Myokines, Measurement, and Technical Considerations

      Willis, Craig R.G.; Deane, C.S.; Etheridge, T. (Humana, 2023-07-31)
      Skeletal muscle has long been established as a highly multifunctional organ, playing a vital role in locomotion, whole-body metabolic and energy homeostasis, and thermoregulation. More recently, emergent evidence has highlighted a potent secretory role for muscle, producing and releasing “myokine” molecules that act in autocrine, paracrine, or endocrine fashion to govern muscle physiology and regulate whole-body homeostasis via multi-tissue cross talk mechanisms. Myokines represent promising therapeutic targets in health and disease, with their discovery, measurement, and functional importance being a hotbed of research across numerous physiological contexts. Here, we provide an overview of myokines and summarize current understanding of their biological role(s). We also outline primary approaches for myokine analysis, including detailed methodology for performing omics-driven myokine prediction, while further appraising both method-specific and general technical considerations to provide an evidence-based approach for designing and conducting myokine experiments.
    • Spaceflight Induces Strength Decline in Caenorhabditis elegans

      Soni, P.; Edwards, H.; Anupom, T.; Rahman, M.; Lesanpezeshki, L.; Blawzdziewicz, J.; Cope, H.; Gharahdaghi, N.; Scott, D.; Toh, L.S.; et al. (2023-10-17)
      Background: Understanding and countering the well-established negative health consequences of spaceflight remains a primary challenge preventing safe deep space exploration. Targeted/personalized therapeutics are at the forefront of space medicine strategies, and cross-species molecular signatures now define the 'typical' spaceflight response. However, a lack of direct genotype-phenotype associations currently limits the robustness and, therefore, the therapeutic utility of putative mechanisms underpinning pathological changes in flight. Methods: We employed the worm Caenorhabditis elegans as a validated model of space biology, combined with 'NemaFlex-S' microfluidic devices for assessing animal strength production as one of the most reproducible physiological responses to spaceflight. Wild-type and dys-1 (BZ33) strains (a Duchenne muscular dystrophy (DMD) model for comparing predisposed muscle weak animals) were cultured on the International Space Station in chemically defined media before loading second-generation gravid adults into NemaFlex-S devices to assess individual animal strength. These same cultures were then frozen on orbit before returning to Earth for next-generation sequencing transcriptomic analysis. Results: Neuromuscular strength was lower in flight versus ground controls (16.6% decline, p
    • Adaptability to eccentric exercise training is diminished with age in female mice

      Baumann, C.W.; Deane, C.S.; Etheridge, T.; Szewczyk, N.J.; Willis, Craig R.G.; Lowe, D.A. (2023-11-01)
      The ability of skeletal muscle to adapt to eccentric contractions has been suggested to be blunted in older muscle. If eccentric exercise is to be a safe and efficient training mode for older adults, preclinical studies need to establish if older muscle can effectively adapt and if not, determine the molecular signatures that are causing this impairment. The purpose of this study was to quantify the extent age impacts functional adaptations of muscle and identify genetic signatures associated with adaptation (or lack thereof). The anterior crural muscles of young (4 mo) and older (28 mo) female mice performed repeated bouts of eccentric contractions in vivo (50 contractions/wk for 5 wk) and isometric torque was measured across the initial and final bouts. Transcriptomics was completed by RNA-sequencing 1 wk following the fifth bout to identify common and differentially regulated genes. When torques post eccentric contractions were compared after the first and fifth bouts, young muscle exhibited a robust ability to adapt, increasing isometric torque 20%-36%, whereas isometric torque of older muscle decreased up to 18% (P ≤ 0.047). Using differential gene expression, young and older muscles shared some common transcriptional changes in response to eccentric exercise training, whereas other transcripts appeared to be age dependent. That is, the ability to express particular genes after repeated bouts of eccentric contractions was not the same between ages. These molecular signatures may reveal, in part, why older muscles do not appear to be as adaptive to exercise training as young muscles.NEW & NOTEWORTHY The ability to adapt to exercise training may help prevent and combat sarcopenia. Here, we demonstrate young mouse muscles get stronger whereas older mouse muscles become weaker after repeated bouts of eccentric contractions, and that numerous genes were differentially expressed between age groups following training. These results highlight that molecular and functional plasticity is not fixed in skeletal muscle with advancing age, and the ability to handle or cope with physical stress may be impaired.
    • VEGF stimulates activation of ERK5 in the absence of C-terminal phosphorylation preventing nuclear localization and facilitating AKT activation in endothelial cells

      Mondru, A.K.; Aljasir, M.A.; Alrumayh, A.; Nithianandarajah, G.N.; Ahmed, K.; Muller, Jurgen; Goldring, C.E.P.; Wilm, B.; Cross, M.J. (2023-03)
      Extracellular-signal-regulated kinase 5 (ERK5) is critical for normal cardiovascular development. Previous studies have defined a canonical pathway for ERK5 activation, showing that ligand stimulation leads to MEK5 activation resulting in dual phosphorylation of ERK5 on Thr218/Tyr220 residues within the activation loop. ERK5 then undergoes a conformational change, facilitating phosphorylation on residues in the C-terminal domain and translocation to the nucleus where it regulates MEF2 transcriptional activity. Our previous research into the importance of ERK5 in endothelial cells highlighted its role in VEGF-mediated tubular morphogenesis and cell survival, suggesting that ERK5 played a unique role in endothelial cells. Our current data show that in contrast to EGF-stimulated HeLa cells, VEGF-mediated ERK5 activation in human dermal microvascular endothelial cells (HDMECs) does not result in C-terminal phosphorylation of ERK5 and translocation to the nucleus, but instead to a more plasma membrane/cytoplasmic localisation. Furthermore, the use of small-molecule inhibitors to MEK5 and ERK5 shows that instead of regulating MEF2 activity, VEGF-mediated ERK5 is important for regulating AKT activity. Our data define a novel pathway for ERK5 activation in endothelial cells leading to cell survival.
    • Talking about falls: a qualitative exploration of spoken communication of patients' fall risks in hospitals and implications for multifactorial approaches to fall prevention.

      McVey, Lynn; Alvarado, Natasha; Healey, F.; Montague, Jane; Todd, C.; Zaman, Hadar; Dowding, D.; Lynch, A.; Issa, B.; Randell, Rebecca (2024-03)
      Inpatient falls are the most common safety incident reported by hospitals worldwide. Traditionally, responses have been guided by categorising patients' levels of fall risk, but multifactorial approaches are now recommended. These target individual, modifiable fall risk factors, requiring clear communication between multidisciplinary team members. Spoken communication is an important channel, but little is known about its form in this context. We aim to address this by exploring spoken communication between hospital staff about fall prevention and how this supports multifactorial fall prevention practice. Data were collected through semistructured qualitative interviews with 50 staff and ethnographic observations of fall prevention practices (251.25 hours) on orthopaedic and older person wards in four English hospitals. Findings were analysed using a framework approach. We observed staff engaging in 'multifactorial talk' to address patients' modifiable risk factors, especially during multidisciplinary meetings which were patient focused rather than risk type focused. Such communication coexisted with 'categorisation talk', which focused on patients' levels of fall risk and allocating nursing supervision to 'high risk' patients. Staff negotiated tensions between these different approaches through frequent 'hybrid talk', where, as well as categorising risks, they also discussed how to modify them. To support hospitals in implementing multifactorial, multidisciplinary fall prevention, we recommend: (1) focusing on patients' individual risk factors and actions to address them (a 'why?' rather than a 'who' approach); (2) where not possible to avoid 'high risk' categorisations, employing 'hybrid' communication which emphasises actions to modify individual risk factors, as well as risk level; (3) challenging assumptions about generic interventions to identify what individual patients need; and (4) timing meetings to enable staff from different disciplines to participate.
    • Pottery

      Copper, Michael (2023-06)
      An interim report on pottery recovered during underwater surveys undertaken around a series of artificial islets on the islands of North and South Uist in 2022.
    • Pottery

      Copper, Michael (2022-08)
      An interim report on pottery excavated at the Neolithic islet of Loch Bhorgastail, Isle of Lewis, Scotland, in 2021.
    • The effect of aspirin and eicosapentaenoic acid on urinary biomarkers of prostaglandin E2 synthesis and platelet activation in participants of the seAFOod polyp prevention trial

      Sun, G.; Fuller, H.; Fenton, H.; Race, Amanda D.; Downing, A.; Williams, E.A.; Rees, C.J.; Brown, L.C.; Loadman, Paul; Hull, M.A. (John Wiley & Sons Ltd, 2024-03)
      Urinary prostaglandin (PG) E metabolite (PGE-M) and 11-dehydro (d)-thromboxane (TX) B2 are biomarkers of cyclooxygenase-dependent prostanoid synthesis. We investigated (1) the effect of aspirin 300 mg daily and eicosapentaenoic acid (EPA) 2000 mg daily, alone and in combination, on urinary biomarker levels and, (2) whether urinary biomarker levels predicted colorectal polyp risk, during participation in the seAFOod polyp prevention trial. Urinary PGE-M and 11-d-TXB2 were measured by liquid chromatography-tandem mass spectrometry. The relationship between urinary biomarker levels and colorectal polyp outcomes was investigated using negative binomial (polyp number) and logistic (% with one or more polyps) regression models. Despite wide temporal variability in PGE-M and 11-d-TXB2 levels within individuals, both aspirin and, to a lesser extent, EPA decreased levels of both biomarkers (74% [P ≤ .001] and 8% [P ≤ .05] reduction in median 11-d-TXB2 values, respectively). In the placebo group, a high (quartile [Q] 2-4) baseline 11-d-TXB2 level predicted increased polyp number (incidence rate ratio [IRR] [95% CI] 2.26 [1.11,4.58]) and risk (odds ratio [95% CI] 3.56 [1.09,11.63]). A low (Q1) on-treatment 11-d-TXB2 level predicted reduced colorectal polyp number compared to placebo (IRR 0.34 [0.12,0.93] for combination aspirin and EPA treatment) compared to high on-treatment 11-d-TXB2 values (0.61 [0.34,1.11]). Aspirin and EPA both inhibit PGE-M and 11-d-TXB2 synthesis in keeping with shared in vivo cyclooxygenase inhibition. Colorectal polyp risk and treatment response prediction by 11-d-TXB2 is consistent with a role for platelet activation during early colorectal carcinogenesis. The use of urinary 11-d-TXB2 measurement for a precision approach to colorectal cancer risk prediction and chemoprevention requires prospective evaluation.
    • Polymorphisms in Cyclooxygenase, Lipoxygenase and TP53 genes predict colorectal polyp risk reduction by aspirin in the seAFOod polyp prevention trial

      Davies, J.R.; Mell, T.; Fuller, H.; Harland, M.; Saleh, R.N.M.; Race, Amanda D.; Rees, C.J.; Brown, L.C.; Loadman, Paul; Downing, A.; et al. (AACR, 2023-11)
      Aspirin and eicosapentaenoic acid (EPA) reduce colorectal adenomatous polyp risk and affect synthesis of oxylipins including prostaglandin E2. We investigated whether 35 single nucleotide polymorphisms (SNPs) in oxylipin metabolism genes such as cyclooxygenase [PTGS] and lipoxygenase [ALOX], as well as 7 SNPs already associated with colorectal cancer (CRC) risk reduction by aspirin (eg. TP53; rs104522), modified the effects of aspirin and EPA on colorectal polyp recurrence in the randomised 2x2 factorial seAFOod trial. Treatment effects were reported as the incidence rate ratio (IRR) and 95% confidence interval (CI) by stratifying negative binomial and Poisson regression analyses of colorectal polyp risk on SNP genotype. Statistical significance was reported with adjustment for the false discovery rate as the P and q value. Five hundred and forty-two (of 707) trial participants had both genotype and colonoscopy outcome data. Reduction in colorectal polyp risk in aspirin users compared with non-aspirin users was restricted to rs4837960 (PTGS1) common homozygotes (IRR 0.69 [95%CI 0.53,0.90]; q=0.06), rs2745557 (PTGS2) compound heterozygote-rare homozygotes (IRR 0.60 [0.41,0.88]; q=0.06), rs7090328 (ALOX5) rare homozygotes (IRR 0.27 [0.11,0.64]; q=0.05), rs2073438 (ALOX12) common homozygotes (IRR 0.57 [0.41,0.80]; q=0.05), and rs104522 (TP53) rare homozygotes (IRR 0.37 [0.17,0.79]; q=0.06). No modification of colorectal polyp risk in EPA users was observed. In conclusion, genetic variants relevant to the proposed mechanism of action on oxylipins are associated with differential colorectal polyp risk reduction by aspirin in individuals who develop multiple colorectal polyps. SNP genotypes should be considered during development of personalised, predictive models of CRC chemoprevention by aspirin.
    • Pottery from BHO16; Pottery from LAN16/17; and The pottery

      Copper, Michael (2019-04)
      This interim report covers archaeological work undertaken at two Neolithic islet sites or crannogs, Loch Bhorgastail and Loch Langabhat, on the Isle of Lewis, Outer Hebrides, from 15-29 July 2017 (Figure 1). Fieldwork in 2017 included photogrammetric survey of both stone-built islets (under and above water), palaeoenvironmental coring of both loch beds, excavation at Loch Langabhat and vegetation clearance at Loch Bhorgastail. This work followed on directly from fieldwork carried out in 2016; the present report should therefore be read in conjunction with that report (Garrow, Sturt & Copper 2017). Our main results for fieldwork in 2017 included: • Construction of detailed 3D photogrammetric models of both sites • A better understanding of the construction techniques used in the creation of both islets • Recovery of c. 0.60m of core material from each loch for palaeoenvironmental assessment • The identification and excavation of occupation deposits and a small structure at Loch Langabhat
    • A conservative party: pots and people in the Hebridean Neolithic

      Copper, Michael; Armit, Ian (2018-10-22)
      Recent analysis of the ceramic assemblage from the Neolithic loch islet settlement of Eilean Dòmhnuill, North Uist, in the Western Isles of Scotland has highlighted the intense conservatism of the potting traditions over a period of more than 800 years. Hebridean Neolithic pottery exhibits clear relationships with pottery from Argyll, Arran, and Bute, as well as Orkney and the north-east mainland of Scotland. It appears to have developed a distinctive, often decoratively elaborate regional form very soon after its initial appearance, which subsequently appears to have undergone little or no significant change until the introduction of Grooved Ware in the early 3rd millennium BC. An association exists between large assemblages of elaborately decorated Hebridean pottery and a number of artificial islets in freshwater lochs, some very small and producing little or no evidence for domestic activities. This might be explained by the importance of commensality in mediating relations between small communities in the Western Isles at such sites following the introduction of agriculture in the 2nd quarter of the 4th millennium BC. The conservatism and stasis evident at Eilean Dòmhnuill, in the face of environmental decline, raises wider issues around the adaptive capabilities of the first farming communities prior to significant social changes in the earlier 3rd millennium BC.
    • Appendix 1: Pottery from Loch Langabhat, Loch Bhorgastail and Loch Arnish

      Copper, Michael (2017-03)
      An interim report on pottery recovered from three loch islet sites in the Outer Hebrides, Scotland, during fieldwork in 2016.
    • Hypoxia-induced SETX links replication stress with the unfolded protein response

      Ramachandran, S.; Ma, T.S.; Griffin, J.; Ng, N.; Foskolou, I.P.; Hwang, M-S.; Victori, P.; Cheng, W-C.; Buffa, F.M.; Leszczynska, K.B.; et al. (2021)
      Tumour hypoxia is associated with poor patient prognosis and therapy resistance. A unique transcriptional response is initiated by hypoxia which includes the rapid activation of numerous transcription factors in a background of reduced global transcription. Here, we show that the biological response to hypoxia includes the accumulation of R-loops and the induction of the RNA/DNA helicase SETX. In the absence of hypoxia-induced SETX, R-loop levels increase, DNA damage accumulates, and DNA replication rates decrease. Therefore, suggesting that, SETX plays a role in protecting cells from DNA damage induced during transcription in hypoxia. Importantly, we propose that the mechanism of SETX induction in hypoxia is reliant on the PERK/ATF4 arm of the unfolded protein response. These data not only highlight the unique cellular response to hypoxia, which includes both a replication stress-dependent DNA damage response and an unfolded protein response but uncover a novel link between these two distinct pathways.
    • High Temperature Drives Topoisomerase Mediated Chromosomal Break Repair Pathway Choice.

      Ashour, M.E.; Allam, W.; Elsayed, W.; Atteya, R.; Elserafy, M.; Magdeldin, S.; Hassan, M.K.; El-Khamisy, Sherif (2021-05)
      Cancer-causing mutations often arise from inappropriate DNA repair, yet acute exposure to DNA damage is widely used to treat cancer. The challenge remains in how to specifically induce excessive DNA damage in cancer cells while minimizing the undesirable effects of genomic instability in noncancerous cells. One approach is the acute exposure to hyperthermia, which suppresses DNA repair and synergizes with radiotherapy and chemotherapy. An exception, however, is the protective effect of hyperthermia on topoisomerase targeting therapeutics. The molecular explanation for this conundrum remains unclear. Here, we show that hyperthermia suppresses the level of topoisomerase mediated single- and double-strand breaks induced by exposure to topoisomerase poisons. We further uncover that, hyperthermia suppresses hallmarks of genomic instability induced by topoisomerase targeting therapeutics by inhibiting nuclease activities, thereby channeling repair to error-free pathways driven by tyrosyl-DNA phosphodiesterases. These findings provide an explanation for the protective effect of hyperthermia from topoisomerase-induced DNA damage and may help to explain the inverse relationship between cancer incidence and temperature. They also pave the way for the use of controlled heat as a therapeutic adjunct to topoisomerase targeting therapeutics.
    • A role for Rad5 in ribonucleoside monophosphate (rNMP) tolerance

      Elserafy, M.; El-Sheikh, I.; Fleifel, D.; Atteya, R.; AlOkda, A.; Abdrabbou, M.M.; Nasr, M.; El-Khamisy, Sherif (2021-08)
      Ribonucleoside monophosphate (rNMP) incorporation in genomic DNA poses a significant threat to genomic integrity. In addition to repair, DNA damage tolerance mechanisms ensure replication progression upon encountering unrepaired lesions. One player in the tolerance mechanism is Rad5, which is an E3 ubiquitin ligase and helicase. Here, we report a new role for yeast Rad5 in tolerating rNMP incorporation, in the absence of the bona fide ribonucleotide excision repair pathway via RNase H2. This role of Rad5 is further highlighted after replication stress induced by hydroxyurea or by increasing rNMP genomic burden using a mutant DNA polymerase (Pol ε - Pol2-M644G). We further demonstrate the importance of the ATPase and ubiquitin ligase domains of Rad5 in rNMP tolerance. These findings suggest a similar role for the human Rad5 homologues helicase-like transcription factor (HLTF) and SNF2 Histone Linker PHD RING Helicase (SHPRH) in rNMP tolerance, which may impact the response of cancer cells to replication stress-inducing therapeutics.
    • Identification and Validation of ERK5 as a DNA Damage Modulating Drug Target in Glioblastoma

      Carmell, N.; Rominiyi, O.; Myers, K.N.; McGarrity-Cottrell, C.; Vanderlinden, A.; Lad, N.; Perroux-David, E.; El-Khamisy, Sherif; Fernando, M.; Finegan, K.G.; et al. (2021-03)
      Brain tumours kill more children and adults under 40 than any other cancer, with approximately half of primary brain tumours being diagnosed as high-grade malignancies known as glioblastomas. Despite de-bulking surgery combined with chemo-/radiotherapy regimens, the mean survival for these patients is only around 15 months, with less than 10% surviving over 5 years. This dismal prognosis highlights the urgent need to develop novel agents to improve the treatment of these tumours. To address this need, we carried out a human kinome siRNA screen to identify potential drug targets that augment the effectiveness of temozolomide (TMZ)-the standard-of-care chemotherapeutic agent used to treat glioblastoma. From this we identified ERK5/MAPK7, which we subsequently validated using a range of siRNA and small molecule inhibitors within a panel of glioma cells. Mechanistically, we find that ERK5 promotes efficient repair of TMZ-induced DNA lesions to confer cell survival and clonogenic capacity. Finally, using several glioblastoma patient cohorts we provide target validation data for ERK5 as a novel drug target, revealing that heightened ERK5 expression at both the mRNA and protein level is associated with increased tumour grade and poorer patient survival. Collectively, these findings provide a foundation to develop clinically effective ERK5 targeting strategies in glioblastomas and establish much-needed enhancement of the therapeutic repertoire used to treat this currently incurable disease.
    • SMN-deficient cells exhibit increased ribosomal DNA damage.

      Karyka, E.; Ramirez, N.B.; Webster, C.P.; Marchi, P.M.; Graves, E.J.; Godena, V.K.; Marrone, L.; Bhargava, A.; Ray, S.; Ning, K.; et al. (2022-08)
      Spinal muscular atrophy, the leading genetic cause of infant mortality, is a motor neuron disease caused by low levels of survival motor neuron (SMN) protein. SMN is a multifunctional protein that is implicated in numerous cytoplasmic and nuclear processes. Recently, increasing attention is being paid to the role of SMN in the maintenance of DNA integrity. DNA damage and genome instability have been linked to a range of neurodegenerative diseases. The ribosomal DNA (rDNA) represents a particularly unstable locus undergoing frequent breakage. Instability in rDNA has been associated with cancer, premature ageing syndromes, and a number of neurodegenerative disorders. Here, we report that SMN-deficient cells exhibit increased rDNA damage leading to impaired ribosomal RNA synthesis and translation. We also unravel an interaction between SMN and RNA polymerase I. Moreover, we uncover an spinal muscular atrophy motor neuron-specific deficiency of DDX21 protein, which is required for resolving R-loops in the nucleolus. Taken together, our findings suggest a new role of SMN in rDNA integrity.
    • Defective repair of topoisomerase I induced chromosomal damage in Huntington's disease

      Palminha, N.M.; Dos Santos Souza, C.; Griffin, J.; Liao, C.; Ferraiuolo, L.; El-Khamisy, Sherif (2022-03)
      Topoisomerase1 (TOP1)-mediated chromosomal breaks are endogenous sources of DNA damage that affect neuronal genome stability. Whether TOP1 DNA breaks are sources of genomic instability in Huntington's disease (HD) is unknown. Here, we report defective 53BP1 recruitment in multiple HD cell models, including striatal neurons derived from HD patients. Defective 53BP1 recruitment is due to reduced H2A ubiquitination caused by the limited RNF168 activity. The reduced availability of RNF168 is caused by an increased interaction with p62, a protein involved in selective autophagy. Depletion of p62 or disruption of the interaction between RNAF168 and p62 was sufficient to restore 53BP1 enrichment and subsequent DNA repair in HD models, providing new opportunities for therapeutic interventions. These findings are reminiscent to what was described for p62 accumulation caused by C9orf72 expansion in ALS/FTD and suggest a common mechanism by which protein aggregation perturb DNA repair signaling.
    • CORM-3 induces DNA damage through Ru(II) binding to DNA

      Lyon, R.F.; Southam, H.M.; Trevitt, C.R.; Liao, C.; El-Khamisy, Sherif; Poole, R.K.; Williamson, M.P. (2022-07-04)
      When the 'CO-releasing molecule-3', CORM-3 (Ru(CO)3Cl(glycinate)), is dissolved in water it forms a range of ruthenium complexes. These are taken up by cells and bind to intracellular ligands, notably thiols such as cysteine and glutathione, where the Ru(II) reaches high intracellular concentrations. Here, we show that the Ru(II) ion also binds to DNA, at exposed guanosine N7 positions. It therefore has a similar cellular target to the anticancer drug cisplatin, but not identical, because Ru(II) shows no evidence of forming intramolecular crossbridges in the DNA. The reaction is slow, and with excess Ru, intermolecular DNA crossbridges are formed. The addition of CORM-3 to human colorectal cancer cells leads to strand breaks in the DNA, as assessed by the alkaline comet assay. DNA damage is inhibited by growth media containing amino acids, which bind to extracellular Ru and prevent its entry into cells. We conclude that the cytotoxicity of Ru(II) is different from that of platinum, making it a promising development target for cancer therapeutics.