A.R. Collins MA, PhD, ScD
Professor of Nutrition Biology
Department of Nutrition, University of Oslo
PB 1046 Blindern, 0316 Oslo, Norway
Email: a.r.collins@medisin.uio.no
Tel.: +47 22851360
Research interests:
My early research was focused on molecular mechanisms of DNA repair in mammalian cells, and in particular the manipulation of repair with the use of DNA synthesis inhibitors, which allowed identification of mutant phenotypes and analysis of the kinetics of repair. I then developed an interest in oxidative damage to DNA, and the ability of phytochemicals to protect against this damage, pioneering a molecular epidemiological approach using the comet assay to measure DNA damage in lymphocytes from human subjects. I co-ordinated an international effort (ESCODD) to deal with serious methodological problems in the measurement of DNA oxidation.
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| The comet assay is a simple method for measuring DNA breaks at the level of single cells |
In my lab in Aberdeen, and now in Oslo, we have carried out numerous human intervention studies, looking at the effects of natural antioxidants, and plant foods rich in antioxidants, on levels of DNA damage in lymphocytes. We have demonstrated in most cases a significant protection against DNA oxidation. However, I have come to doubt the biological significance of improving antioxidant status - in line with the emerging picture from clinical trials where disease or death is the endpoint; these show on the whole no effect of antioxidant supplements, or even a deleterious effect.
It remains true that consumption of fruits and vegetables seems to protect against cancer, but there are many metabolic roles that phytochemicals play, other than antioxidant protection. One such role is the modulation of DNA repair - the cell's main protection against DNA damage producing mutations. Recently we have demonstrated enhanced DNA repair activity following dietary supplementation with fruits.
We have developed high throughput biomarker assays for DNA damage and repair for use in large-scale human trials, in combination with genotyping. Future efforts will emphasise interactions of environment (including nutrition) with DNA repair phenotype and genotype.We are also validating a modified approach to genotoxicity testing with the comet assay, giving extra sensitivity without loss of specificity. This should allow identification of potentially carcinogenic chemicals that do not directly cause DNA strand breaks; such chemicals are at present hard to detect with the standard comet assay.
In the COMICS project, we developed high throughput comet assay methods, applicable to human biomonitoring, ecogenotoxicology, and genotoxicity testing.
- ComNet, a network of researcher using the comet assay in human biomonitoring
- EcoGenoTox, which seeks a unified practical approach to biomonitoring, genotoxicity testing and ecogenotoxicology
- Comet Biotech AS, a company set up by individual researchers in Norway, with backing from Innven2, and the Norwegian Institute for Air Research (NILU).
Recent Publications:
Collins,A.R. and Azqueta,A. (2012) DNA repair as a biomarker in human biomonitoring studies; further applications of the comet assay. Mutation Res. 736,122-129
Møller,P., Cooke,M.S., Collins,A., Olinski,R., Rozalski,R. and Loft,S. (2012) Harmonising measurements of 8-oxo-7,8-dihydro-2’- deoxyguanosine in cellular DNA and urine. Free Rad. Res. 46, 541-553.
Mladinic,M., Zeljezic,D., Shaposhnikov,S.A., Collins,A.R. (2012) The use of FISH-comet to detect c-Myc and TP 53 damage in extended-term lymphocyte cultures treated with terbuthylazine and carbofuran. Toxicol. Lett. 211, 62-69
Collins,A.R., Azqueta,A., Langie,S.A.S. (2012) Effects of micronutrients on DNA repair. Eur. J. Nutr. 51, 261-279
Collins,A.R., Ferguson, L.R. (2012) DNA repair as a biomarker. Mutat. Res. 736, 2-4
Azqueta,A., Collins,A.R. (2012) Carotenoids and DNA damage. Mutat. Res. 733, 4-13.
Dusinska,M., Staruchova,M., Horska,A., Smolkova,B., Collins,A.R., Bonassi,S., Volkovova, K. (2012) Are glutathione S transferases involved in DNA damage signalling? Interactions with DNA damage and repair revealed from molecular epidemiology studies, Mutat. Res. 736, 130-137.
Dolara,P., Bigagli,E., Collins,A. (2012) Antioxidant vitamins and mineral supplementation, life span expansion and cancer incidence: a critical commentary, Eur. J. Nut. 51, 769-781.
Collins,A., Anderson,D., Coskun,E., Dhawan,A., Dusinska,M., Koppen,G., Kruszewski,M., Moretti,M., Rojas,E., Speit,G., Valverde,M., Bonassi,S. (2012) Launch of the ComNet (comet network) project on the comet assay in human population studies during the International Comet Assay Workshop meeting in Kusadasi, Turkey (September 13-16, 2011). Mutagenesis, 27, 385-386
Magdolenova,Z., Lorenzo,Y., Collins,A., Dusinska,M. (2012) Can standard genotoxicity tests be applied to nanoparticles? J. Toxicol. Env. Health Pt A: Current Issues, 75, 800-806
Ramos,A.A., Pedro,D., Collins,A.R., Pereira-Wilson,C. (2012) Protection by Salvia extracts against oxidative and alkylation damage to DNA in human HCT15 and CO115 cells. J. Toxicol. Env. Health Pt A: Current Issues, 75, 765-775
Hudecova,A., Kusnierewicz,B., Runden-Pran,E., Magdolenova,Z., Hasplova,K., Rinna,A., Fjellsbø,L.M., Kruszewski,M., Lankoff,A., Sandberg,W.J., Refsnes,M., Skuland,T., Schwarze,P., Brunborg,G., Bjøras,M., Collins,A., Miadokova,E., Galova,E., Dusinska,M. (2012) Silver nanoparticles induce pre-mutagenic DNA oxidation that can be prevented by phytochemicals from Gentiana asclepiadea. Mutagenesis, 27, 759-769
Slyskova,J., Korenkova,V.,Collins,A.R., Prochazka,P., Vodickova,L., Svec,J., Lipska,L., Levy,M., Schneiderova,M., Liska,V., Holubec,L., Kumar,R., Soucek,P., Naccarati,A., Vodicka,P. (2012) Functional, genetic and epigenetic aspects of base and nucleotide excision repair in colorectal carcinomas. Clin. Cancer Res. 18, 5878-5887
Solhaug,A., Vines,L.L., Ivanova,L., Spilsberg,B., Holme,J.A., Pestka,J., Collins,A., Eriksen,G.S. (2012) Mechanisms involved in alternariol-induced cell cycle arrest. Mutat. Res. 738-739, 1-11
Hudecova, A., Hasplova, K., Miadokova, E., Magdolenova, Z., Rinna, A., Collins, A., Galova, E., Vaculcikova, D., Gregan, F., Dusinska, M. (2012)
Gentiana asclepiadea protects human cells against oxidation DNA lesions. Cell Biochem. Funct. 30, 101-107
Osnes-Ringen, Ø., Azqueta, A., Moe, M.C., Zetterström, C., Røger, M., Nicolaissen, B., Collins, A.R. (2013) DNA damage in lens epithelium of cataract patients in vivo and ex vivo. Acta Ophthalm. 91, 652-656
Haug,K., Azqueta,A., Johnsen-Soriano, S.,Shahdadfar,A., Drolsum,L.K., Moe,M.C., Røger,M.T., Romero,F.J., Collins,A.R., Nicolaissen,B. (2013) Donor cornea transfer from Optisol GS to organ culture storage: a two-step procedure to increase donor tissue lifespan. Acta Ophthalm. 91, 219-225.
Azqueta,A., Arbillaga,L., Lopez de Cerain,A., Collins,A. (2013) Enhancing the sensitivity of the comet assay as a genotoxicity test, by combining it with bacterial repair enzyme FPG. Mutagenesis 28, 271-277
Azqueta,A., Gutzkow,K.B., Priestley,C.C., Meier,S., Walker,J.S., Brunborg,G., Collins,A.R. (2013) A comparative performance test of standard, medium and high throughput comet assays. Toxicology in Vitro 27, 768-773
Gutzkow,K.B., Langleite,T.M., Meier,S., Graupner,A., Collins,A., Brunborg,G. (2013) High throughput comet assay using 96 minigels. Mutagenesis 28, 333-340.
Ersson,C., Møller,P., Forchhammer,L., Loft,S., Azqueta,A.,…Collins,A.R., Möller,L. (2013) An ECVAG inter-laboratory validation study of the comet assay: inter-laboratory and intra-laboratory variations of DNA strand breaks and FPG-sensitive sites in human mononuclear cells. Mutagenesis 28, 279-286.
Lorenzo,Y., Costa,S., Collins,A.R., Azqueta,A. (2013) The comet assay, DNA damage, DNA repair and cytotoxicity: hedgehogs are not always dead. Mutagenesis 28, 427-432
Azqueta,A., Collins,A.R. (2013) The essential comet assay: a comprehensive guide to measuring DNA damage and repair. Arch. Toxicol. 87, 949-968
Ramos,A.A., Pedro,D.F., Lima,C.F., Collins,A.R., Pereira-Wilson,C. (2013) Development of a new application of the comet assay to assess levels of O6-methylguanine in genomic DNA. Free Rad. Biol. Med., 60, 41-48
Azqueta,A., Costa,S., Lorenzo,Y., Bastani,N.E., Collins,A.R. (2013) Vitamin C in cultured human (HeLa) cells: Lack of effect on DNA protection and repair. Nutrients, 5,1200-1217
Collins,A.R. (2013) Kiwifruit as a modulator of DNA damage and repair. Adv. Food Nutr. Res. 68, 283-299
Magdolenova,Z., Collins,A., Kumar,A., Dhawan,A., Stone,V., Dusinska,M. (2014) Mechanisms of genotoxicity. A review of in vitro and in vivo studies with engineered nanoparticles. Nanotoxicology 8, 233-278
Collins,A.R. (2014) Measuring oxidative damage to DNA and its repair with the comet assay. Biochim. Biophys. Acta 1840, 794-800
Details of Projects:
The ComNet project
ComNet is open to all resarchers
using the comet assay as a biomarker for DNA damage or DNA repair in humans. Please
visit the web site, www.comnetproject.org for
information on how to join the network.
The ultimate aim of ComNet is to establish the comet assay
as a reliable, trusted DNA damage assay in human biomonitoring. It is widely
used at present, to assess occupational/ environmental exposure, to test the
effectiveness of dietary modulation in counteracting DNA damage, and to look
at, for example, changes in background levels of DNA damage with age, or disease.
A less common application is the investigation of DNA repair capacity. Because
of a lack of standard protocols, it can be very difficult to compare results
obtained in different laboratories. It is unrealistic to expect everyone to use
exactly the same protocol, but at least we should identify the experimental
factors that are most critical in determining the results of a comet assay
experiment.
As a first step, we are creating
a database of all identifiable human population studies employing the comet
assay. We will send out a questionnaire to collect information about the
methods used, numbers of subjects, selection criteria, aim of study, etc. We
will then collect published results from these studies, and attempt a pooled
analysis of the combined dataset to establish some basic parameters, such as
differences between the sexes, effect of age, smoking, etc.
At the same time, we will work
towards a set of guidelines for using the comet assay, to ensure that in future
the comparison of different studies will be easier and more reliable. We will
invite ComNet members to take part in a validation trial, analysing identical
samples in different labs.
EcoGenoTox
The purpose of EcoGenoTox is to establish a network of experts within
the field of genotoxicology, relating both to human health and the natural
environment.
The aim is then to provide research, expertise, services and new methods
development in the field of environmental (geno)toxicology at both national and
international levels.
The first EcoGenoTox Workshop meeting was held at the Norwegian
Institute for Air Research (NILU) on April 28, 2011. The aim of the
meeting was to bring together scientists, representatives of industry
and regulatory bodies. The program of the workshop covered a number of
topics, including identifying a battery of tests for future development
as tools for use in:
• testing chemicals for genotoxicity, e.g. under the REACH programme
• monitoring genotoxic effects on sentinel organisms in the natural environment
• human biomonitoring
• testing chemicals for genotoxicity, e.g. under the REACH programme
• monitoring genotoxic effects on sentinel organisms in the natural environment
• human biomonitoring
We resolved to focus on a unified approach to genotoxicity testing, human biomonitoring and ecogenotoxicology, since the assays used are common, and considerations such as the need for validation and standardisation apply to all.
There is an increasing awareness of the potential risks from man-made chemicals and other substances to the environment and health. We provide research expertise and selected state-of-the-art genotoxicity assays. Such assays are needed for basic research into genome damage and maintenance, for regulatory purposes (testing chemicals for possible health effects and under the REACH programme), for testing novel industrial products, and for biomonitoring.
Comet Biotech AS
provides the
latest, state-of-the-art, high throughput assays targeted at the chemical
industry, cosmetic and pharmaceutical companies, regulatory bodies, the REACH
programme, basic genome research and biomonitoring projects.
Toxicity testing
There is an increasing awareness of the potential risks from man-made chemicals and other substances to the environment and health. We provide research expertise and selected state-of-the-art genotoxicity assays. Such assays are needed for basic research into genome damage and maintenance, for regulatory purposes (testing chemicals for possible health effects and under the REACH programme), for testing novel industrial products, and for biomonitoring.
Partnership in research projects
With our background in academic research, we are keen to continue to act as SME-partners in research projects, funded by the EC or other research organisations. We have experience in running small scale human nutritional intervention studies, including planning, obtaining ethical approval, collecting and processing samples, administering supplements, and analysing various biomarkers.
The comet assay
The core interest of the company is the comet assay, but we also offer a range of additional assays for genotoxicity and cytotoxicity. Over a period of almost two decades, the company’s founders have adapted the comet assay in many different ways, extending the kinds of DNA damage detected, increasing sensitivity, applying the assay in human biomonitoring, developing assays for DNA repair, and most recently producing high throughput versions of the assay. Our move to a commercial environment allows us to exploit these innovations fully.
With our background in academic research, we are keen to continue to act as SME-partners in research projects, funded by the EC or other research organisations. We have experience in running small scale human nutritional intervention studies, including planning, obtaining ethical approval, collecting and processing samples, administering supplements, and analysing various biomarkers.
The comet assay
The core interest of the company is the comet assay, but we also offer a range of additional assays for genotoxicity and cytotoxicity. Over a period of almost two decades, the company’s founders have adapted the comet assay in many different ways, extending the kinds of DNA damage detected, increasing sensitivity, applying the assay in human biomonitoring, developing assays for DNA repair, and most recently producing high throughput versions of the assay. Our move to a commercial environment allows us to exploit these innovations fully.
Comet assay and cell array for fast and efficient genotoxicity testing
NewGeneris Project: Newborns and Genotoxic exposure risks
http://www.newgeneris.org/Default.aspx?tabid=120
