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Michael Fenech

Varinderpal S Dhillon, Dimitrios Zabaras, Theodora Almond, Paul Cavuoto, Genevieve James-Martin, Michael Fenech
SCOPE: Whey protein isolate (WPI) contains vitamin B12 and folate. However, the efficacy of WPI as a bio-available source of these vitamins in the elderly with low vitamin B12 was not previously tested. We investigated the effects of WPI supplementation on vitamin B12 and folate status in blood and measured changes in homocysteine, methylmalonic acid and genome integrity biomarkers in elderly individuals with low vitamin B12 status. The effect of WPI was compared to soy protein isolate (SPI)...
December 16, 2016: Molecular Nutrition & Food Research
Michael Fenech, Armen Nersesyan, Siegfried Knasmueller
Formaldehyde (FAL) is classified as a Class I carcinogen by the WHO International Agency for Research on Cancer. Therefore, there is a need to validate appropriate methods for detecting its genotoxic effects in vivo in humans. One of the most commonly used methods to measure the genotoxic effects of exposure to environmental chemicals is the lymphocyte cytokinesis-block micronucleus (L-CBMN assay). We performed a systematic review and statistical analysis of the results from all of the published studies in which the L-CBMN assay was used to measure the genotoxic effects of human exposure to FAL...
October 2016: Mutation Research
Michael Fenech, Siegfried Knasmueller, Claudia Bolognesi, Stefano Bonassi, Nina Holland, Lucia Migliore, Fabrizio Palitti, Adayapalam T Natarajan, Micheline Kirsch-Volders
The purpose of this review is to summarise current knowledge on the molecular mechanisms by which in vivo exposure to exogenous chemical genotoxins in humans induces micronuclei (MNi) and other nuclear anomalies in lymphocytes in vivo and ex vivo after nuclear division in vitro. MNi originate from acentric chromosome fragments and/or whole chromosomes that are unable to engage with the mitotic spindle and/or fail to segregate properly to the daughter nuclei during anaphase. The lagging fragments or whole chromosomes are surrounded by membrane and become MNi...
October 2016: Mutation Research
Armen Nersesyan, Michael Fenech, Claudia Bolognesi, Miroslav Mišík, Tahereh Setayesh, Georg Wultsch, Stefano Bonassi, Philip Thomas, Siegfried Knasmüller
This article concerns the use of the lymphocyte cytokinesis-block micronucleus (CBMN) assay in biomonitoring of occupational and environmental exposures to genotoxic agents. Furthermore, we evaluated the use of this method in different exposure scenarios, in comparison to other DNA damage biomarkers and its regional distribution. So far ca. 400 studies have been published and the number increased substantially in the last years. The most frequently investigated groups are hospital personnel, followed by workers in the chemical industry and agricultural workers...
October 2016: Mutation Research
Claudia Bolognesi, Siegfried Knasmueller, Armen Nersesyan, Paola Roggieri, Marcello Ceppi, Marco Bruzzone, Ewa Blaszczyk, Danuta Mielzynska-Svach, Mirta Milic, Stefano Bonassi, Danieli Benedetti, Juliana Da Silva, Raphael Toledo, Daisy Maria Fávero Salvadori, Helena Groot de Restrepo, Metka Filipic, Klara Hercog, Ayça Aktaş, Sema Burgaz, Michael Kundi, Tamara Grummt, Philip Thomas, Maryam Hor, Maria Escudero-Fung, Nina Holland, Michael Fenech
The buccal micronucleus cytome (BMNcyt) assay in uncultured exfoliated epithelial cells from oral mucosa is widely applied in biomonitoring human exposures to genotoxic agents and is also proposed as a suitable test for prescreening and follow-up of precancerous oral lesions. The main limitation of the assay is the large variability observed in the baseline values of micronuclei (MNi) and other nuclear anomalies mainly related to different scoring criteria. The aim of this international collaborative study, involving laboratories with different level of experience, was to evaluate the inter- and intra-laboratory variations in the BMNcyt parameters, using recently implemented guidelines, in scoring cells from the same pooled samples obtained from healthy subjects (control group) and from cancer patients undergoing radiotherapy (treated group)...
September 26, 2016: Mutagenesis
Clint Mizzi, Eleni Dalabira, Judit Kumuthini, Nduna Dzimiri, Istvan Balogh, Nazli Başak, Ruwen Böhm, Joseph Borg, Paola Borgiani, Nada Bozina, Henrike Bruckmueller, Beata Burzynska, Angel Carracedo, Ingolf Cascorbi, Constantinos Deltas, Vita Dolzan, Anthony Fenech, Godfrey Grech, Vytautas Kasiulevicius, Ľudevít Kádaši, Vaidutis Kučinskas, Elza Khusnutdinova, Yiannis L Loukas, Milan Macek, Halyna Makukh, Ron Mathijssen, Konstantinos Mitropoulos, Christina Mitropoulou, Giuseppe Novelli, Ioanna Papantoni, Sonja Pavlovic, Giuseppe Saglio, Jadranka Setric, Maja Stojiljkovic, Andrew P Stubbs, Alessio Squassina, Maria Torres, Marek Turnovec, Ron H van Schaik, Konstantinos Voskarides, Salma M Wakil, Anneke Werk, Maria Del Zompo, Branka Zukic, Theodora Katsila, Ming Ta Michael Lee, Alison Motsinger-Rief, Howard L Mc Leod, Peter J van der Spek, George P Patrinos
Pharmacogenomics aims to correlate inter-individual differences of drug efficacy and/or toxicity with the underlying genetic composition, particularly in genes encoding for protein factors and enzymes involved in drug metabolism and transport. In several European populations, particularly in countries with lower income, information related to the prevalence of pharmacogenomic biomarkers is incomplete or lacking. Here, we have implemented the microattribution approach to assess the pharmacogenomic biomarkers allelic spectrum in 18 European populations, mostly from developing European countries, by analyzing 1,931 pharmacogenomics biomarkers in 231 genes...
2016: PloS One
Maxime François, Wayne Richard Leifert, Jane Hecker, Jeffrey Faunt, Michael Felix Fenech
Guanine-quadruplexes (G4) are highly stable DNA secondary structures known to mediate gene regulation and to trigger genomic instability events during replication. G4 are known to be associated with DNA damage and we propose that G4 are involved in the ageing disorder mild cognitive impairment (MCI). Lymphocytes were obtained from healthy controls and individuals with MCI. The intensity and frequency of G4 foci as well as γH2AX (a marker of DNA damage) intensity were measured by quantitative immunofluorescence and were correlated with cognitive function and cytokinesis-block micronucleus cytome markers of DNA damage...
October 2016: DNA Repair
Xiayu Wu, Neng Cao, Michael Fenech, Xu Wang
Genomic instability and epigenetic alterations are distinct hallmarks shared by cancer and aging. Sirtuins (SIRTs) are class III histone deacetylases that regulate gene expression in response to cellular metabolic status. SIRTs can modulate chromatin function through direct deacetylation of histones and by promoting altered methylation of histones and DNA, leading to repression of transcription. They can also interact and deacetylate a broad range of transcription factors and coregulators, thereby regulating target gene expression both positively and negatively...
October 2016: DNA and Cell Biology
Xiayu Wu, Weijiang Xu, Tao Zhou, Neng Cao, Juan Ni, Tianning Zou, Ziqing Liang, Xu Wang, Michael Fenech
Folate-mediated one-carbon metabolism (FMOCM) is linked to DNA synthesis, methylation, and cell proliferation. Vitamin B6 (B6) is a cofactor, and genetic polymorphisms of related key enzymes, such as serine hydroxymethyltransferase (SHMT), methionine synthase reductase (MTRR), and methionine synthase (MS), in FMOCM may govern the bioavailability of metabolites and play important roles in the maintenance of genomic stability and cell viability (GSACV). To evaluate the influences of B6, genetic polymorphisms of these enzymes, and gene-nutrient interactions on GSACV, we utilized the cytokinesis-block micronucleus assay (CBMN) and PCR-restriction fragment length polymorphism (PCR-RFLP) techniques in the lymphocytes from female breast cancer cases and controls...
June 24, 2016: International Journal of Molecular Sciences
Eric K Yeoh, Robin Krol, Varinderpal S Dhillon, Rochelle Botten, Addolorata Di Matteo, Julie Butters, Aleisha R Brock, Adrian Esterman, Carolyn Salisbury, Michael Fenech
Background Chronic gastrointestinal (GI) morbidity occurs in ≥50% of patients after external beam radiotherapy (EBRT) for carcinoma of prostate (CaP). This prospective, longitudinal study examines which baseline measurements of: 1) homocysteine and micronutrients in plasma; 2) chromosome damage/misrepair biomarkers; and 3) anal and rectal dose volume metrics predict GI morbidity after EBRT. Patients and methods In total, 106 patients with CaP had evaluations of GI symptoms (modified LENT-SOMA questionnaires) before EBRT and at one month, one, two and three years after its completion...
May 2016: Acta Oncologica
Anne Barden, Nathan O'Callaghan, Valerie Burke, Emile Mas, Lawrence J Beilin, Michael Fenech, Ashley B Irish, Gerald F Watts, Ian B Puddey, Rae-Chi Huang, Trevor A Mori
DNA telomere shortening associates with the age-related increase cardiovascular disease (CVD) risk. Reducing oxidative stress, could modify telomere erosion during cell replication, and CVD risk in patients with chronic kidney disease (CKD). The effect of n-3 fatty acids and coenzyme Q10 (CoQ) on telomere length was studied in a double-blind placebo-controlled trial in CKD. Eighty-five CKD patients were randomized to: n-3 fatty acids (4 g); CoQ (200 mg); both supplements; or control (4 g olive oil), daily for 8 weeks...
March 19, 2016: Nutrients
Chibuisi G Alimba, Varinderpal Dhillon, Adekunle A Bakare, Michael Fenech
Heavy metal exposure or dietary deficiency is associated with increased genetic damage, cancer and age-related diseases. Folate (vitamin B9) required for DNA repair and synthesis may increase cellular susceptibility to metal induced genotoxicity. This study investigated the interactive effects of folic acid deficiency and sufficiency on genome instability and cytotoxicity induced by chromium (VI), copper (II), manganese (II), lead (IV), and their mixture (CCMP) in WIL2-NS human B lymphoblastoid cells. WIL2-NS cells were cultured in folic acid deficient (20 nM) and replete (2000 nM) RPMI 1640 medium treated with different concentrations (0...
March 2016: Mutation Research. Genetic Toxicology and Environmental Mutagenesis
Maxime François, Michael F Fenech, Philip Thomas, Maryam Hor, Alan Rembach, Ralph N Martins, Stephanie R Rainey-Smith, Colin L Masters, David Ames, Christopher C Rowe, S Lance Macaulay, Andrew F Hill, Wayne R Leifert, The Australian Imaging Biomarkers And Lifestyle Study Research Group
Alzheimer's disease (AD) is a degenerative brain disorder and is the most common form of dementia. Minimally invasive approaches are required that combine biomarkers to identify individuals who are at risk of developing mild cognitive impairment (MCI) and AD, to appropriately target clinical trials for therapeutic discovery as well as lifestyle strategies aimed at prevention. Buccal mucosa cells from the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing cohort (n=60) were investigated for cytological markers that could be used to identify both MCI and AD individuals...
2016: Current Alzheimer Research
Maxime François, Wayne Richard Leifert, Ross Tellam, Michael Felix Fenech
G-quadruplexes (G4) are highly stable tetra-stranded DNA secondary structures known to mediate gene regulation and to trigger genomic instability events during replication. G4 structural stability can be affected by DNA methylation and oxidation modifications; thus nutrients such as folate that have the ability to alter these processes could potentially modify the genomic occurrence of G4 elements. Hela cells were cultured in a range of folate concentrations or in the presence or absence of 5-aza-2'-deoxycytidine, a DNA-methyltransferase inhibitor...
July 2016: Mutagenesis
Michael Fenech
No abstract text is available yet for this article.
2015: Journal of Nutritional Science and Vitaminology
Claudia Bolognesi, Stefano Bonassi, Siegfried Knasmueller, Michael Fenech, Marco Bruzzone, Cecilia Lando, Marcello Ceppi
The micronucleus assay in uncultured exfoliated buccal mucosa cells, involving minimally invasive sampling, was successfully applied to evaluate inhalation and local exposure to genotoxic agents, impact of nutrition and lifestyle factors. The potential use of the assay in clinics to monitor the development of local oral lesions and as an early biomarker for tumors and different chronic disorders was also investigated. A systematic review of the literature was carried out focusing on the clinical application of the assay...
October 2015: Mutation Research. Reviews in Mutation Research
Mohammad Sabbir Siddiqui, Maxime François, Michael F Fenech, Wayne R Leifert
One of the earliest cellular responses to DNA double strand breaks (DSBs) is the phosphorylation of the core histone protein H2AX (termed γH2AX). Persistent γH2AX is the level of γH2AX above baseline, measured at a given time-point beyond which DNA DSBs are normally expected to be repaired (usually persist for days to months). This review summarizes the concept of persistent γH2AX in the context of exogenous source induced DNA DSBs (e.g. ionizing radiation (IR), chemotherapeutic drugs, genotoxic agents), and endogenous γH2AX levels in normal aging and accelerated aging disorders...
October 2015: Mutation Research. Reviews in Mutation Research
Lynn B Bailey, Patrick J Stover, Helene McNulty, Michael F Fenech, Jesse F Gregory, James L Mills, Christine M Pfeiffer, Zia Fazili, Mindy Zhang, Per M Ueland, Anne M Molloy, Marie A Caudill, Barry Shane, Robert J Berry, Regan L Bailey, Dorothy B Hausman, Ramkripa Raghavan, Daniel J Raiten
The Biomarkers of Nutrition for Development (BOND) project is designed to provide evidence-based advice to anyone with an interest in the role of nutrition in health. Specifically, the BOND program provides state-of-the-art information and service with regard to selection, use, and interpretation of biomarkers of nutrient exposure, status, function, and effect. To accomplish this objective, expert panels are recruited to evaluate the literature and to draft comprehensive reports on the current state of the art with regard to specific nutrient biology and available biomarkers for assessing nutrients in body tissues at the individual and population level...
July 2015: Journal of Nutrition
Wayne R Leifert, Tori Nguyen, Alan Rembach, Ralph Martins, Stephanie Rainey-Smith, Colin L Masters, David Ames, Christopher C Rowe, S Lance Macaulay, Maxime François, Michael F Fenech
Mild cognitive impairment (MCI) may reflect early stages of neurodegenerative disorders such as Alzheimer's disease (AD). Our hypothesis was that cytokeratin 14 (CK14) expression could be used with blood-based biomarkers such as homocysteine, vitamin B12, and folate to identify individuals with MCI or AD from the Australian Imaging, Biomarkers and Lifestyle (AIBL) flagship study of aging. Buccal cells from 54 individuals were analyzed by a newly developed method that is rapid, automated, and quantitative for buccal cell CK14 expression levels...
2015: Journal of Alzheimer's Disease: JAD
Sau Lai Lee, Philip Thomas, Michael Fenech
Successful maintenance of metabolic systems relating to accurate DNA replication and repair is critical for optimal lifelong human health. Should this homeostatic balance become impaired, genomic instability events can arise, compromising the integrity of the genome, which may result in gene expression and human disease. Both genome instability and micronutrient imbalance have been identified and implicated in diseases associated with accelerated ageing which potentially leads to an increased risk for the future development of clinically defined neurodegenerative disorders...
June 2015: Mutation Research
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