TY - JOUR
T1 - DNA repair as a human biomonitoring tool
T2 - Comet assay approaches
AU - Azqueta, Amaya
AU - Langie, Sabine A. S.
AU - Boutet-Robinet, Elisa
AU - Duthie, Susan
AU - Ladeira, Carina
AU - Moller, Peter
AU - Collins, Andrew R.
AU - Godschalk, Roger W. L.
AU - Working Group 5 of the hCOMET project (CA15132)
N1 - Funding Information:
We thank the hCOMET project (COST Action, CA 15132) for support. A.A. thanks the Ministry of Economy, Industry and Competitiveness (‘Ramón y Cajal’ programme, RYC2013-14370) of the Spanish Government for personal support.
Publisher Copyright:
© 2019 Elsevier B.V.
PY - 2019
Y1 - 2019
N2 - The comet assay offers the opportunity to measure both DNA damage and repair. Various comet assay based methods are available to measure DNA repair activity, but some requirements should be met for their effective use in human biomonitoring studies. These conditions include i) robustness of the assay, ii) sources of inter- and intra-individual variability must be known, iii) DNA repair kinetics should be assessed to optimize sampling timing; and iv) DNA repair in accessible surrogate tissues should reflect repair activity in target tissues prone to carcinogenic effects. DNA repair phenotyping can be performed on frozen and fresh samples, and is a more direct measurement than genomic or transcriptomic approaches. There are mixed reports concerning the regulation of DNA repair by environmental and dietary factors. In general, exposure to genotoxic agents did not change base excision repair (BER) activity, whereas some studies reported that dietary interventions affected BER activity. On the other hand, in vitro and in vivo studies indicated that nucleotide excision repair (NER) can be altered by exposure to genotoxic agents, but studies on other life style related factors, such as diet, are rare. Thus, crucial questions concerning the factors regulating DNA repair and inter-individual variation remain unanswered. Intra-individual variation over a period of days to weeks seems limited, which is favourable for DNA repair phenotyping in biomonitoring studies. Despite this reported low infra-individual variation, timing of sampling remains an issue that needs further investigation. A correlation was reported between the repair activity in easily accessible peripheral blood mononuclear cells (PBMCs) and intemal organs for both NER and BER. However, no correlation was found between tumour tissue and blood cells. In conclusion, although comet assay based approaches to measure BER/NER phenotypes are feasible and promising, more work is needed to further optimize their application in human biomonitoring and intervention studies.
AB - The comet assay offers the opportunity to measure both DNA damage and repair. Various comet assay based methods are available to measure DNA repair activity, but some requirements should be met for their effective use in human biomonitoring studies. These conditions include i) robustness of the assay, ii) sources of inter- and intra-individual variability must be known, iii) DNA repair kinetics should be assessed to optimize sampling timing; and iv) DNA repair in accessible surrogate tissues should reflect repair activity in target tissues prone to carcinogenic effects. DNA repair phenotyping can be performed on frozen and fresh samples, and is a more direct measurement than genomic or transcriptomic approaches. There are mixed reports concerning the regulation of DNA repair by environmental and dietary factors. In general, exposure to genotoxic agents did not change base excision repair (BER) activity, whereas some studies reported that dietary interventions affected BER activity. On the other hand, in vitro and in vivo studies indicated that nucleotide excision repair (NER) can be altered by exposure to genotoxic agents, but studies on other life style related factors, such as diet, are rare. Thus, crucial questions concerning the factors regulating DNA repair and inter-individual variation remain unanswered. Intra-individual variation over a period of days to weeks seems limited, which is favourable for DNA repair phenotyping in biomonitoring studies. Despite this reported low infra-individual variation, timing of sampling remains an issue that needs further investigation. A correlation was reported between the repair activity in easily accessible peripheral blood mononuclear cells (PBMCs) and intemal organs for both NER and BER. However, no correlation was found between tumour tissue and blood cells. In conclusion, although comet assay based approaches to measure BER/NER phenotypes are feasible and promising, more work is needed to further optimize their application in human biomonitoring and intervention studies.
KW - DNA repair
KW - Comet assay
KW - Human biomonitoring
KW - Validation
KW - NUCLEOTIDE-EXCISION-REPAIR
KW - OXIDATIVELY DAMAGED DNA
KW - MEASURED IN-VITRO
KW - BASE EXCISION
KW - INTERINDIVIDUAL VARIATION
KW - HUMAN-LYMPHOCYTES
KW - STRAND BREAKS
KW - DIETARY SUPPLEMENTATION
KW - ANTIOXIDANT PROTECTION
KW - INCISION ACTIVITY
U2 - 10.1016/j.mrrev.2019.03.002
DO - 10.1016/j.mrrev.2019.03.002
M3 - (Systematic) Review article
C2 - 31416580
SN - 1383-5742
VL - 781
SP - 71
EP - 87
JO - Mutation Research-Reviews in Mutation Research
JF - Mutation Research-Reviews in Mutation Research
IS - 2019
ER -