Lymphocyte-based challenge DNA-repair assays for personalized health risk assessment

• Published in: Mutation research. Reviews in mutation research Vol. 790; p. 108427
• Main Authors: Wang, Tong-shuai, Ruchirawat, Mathuros, Narasumrit, Panida, Xia, Zhao-lin, Au, William W.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.07.2022
• Subjects: Biomarkers; Challenge assay; Comet assay; Cytokinesis-block micronucleus (CBMN) assay; DNA; DNA Damage - genetics; DNA Repair - genetics; DNA repair capacity; Human biomonitoring; Humans; Lymphocytes; Micronucleus Tests - methods; Neoplasms; Risk Assessment; Human biomonitoring; DNA repair capacity; Challenge assay; Comet assay; Cytokinesis-block micronucleus (CBMN) assay
• ISSN: 1383-5742; 1388-2139
• DOI: 10.1016/j.mrrev.2022.108427

Combinations of genetic and environmental factors are responsible for the development of many human diseases, such as cancer, as demonstrated using various biomarkers. Within this scenario, DNA repair holds a gate-keeper position which determines outcomes after appearance of DNA damage and, therefore, adverse cellular consequences, e.g., initiation of carcinogenesis. DNA repair deficiency and some of the subsequent events can be validated from studies using live cells from cancer patients. However, these deficiencies/events are difficult to demonstrate in live cells from normal individuals because individual variations in DNA repair capacities (DRC) are too low to be measured easily. Such lack of information has been hindering progress in developing personalized disease prevention and intervention protocols, especially among exposed populations. However, using a variety of challenge assays as biomarkers, variations in individual’s DRC can be amplified in live cells and be determined. Furthermore, evidence indicates that DRC are not only inherited but can also be modified by environmental factors (e.g., nutritional status and exposure to genotoxic substances). Using these challenge assays, e.g., in live lymphocytes, individual’s DRC can be holistically and functionally determined as well as quantitated. With the more precise information, assessment of health risk can be better determined on an individual rather than on a population basis. This review provides a succinct summary on the development and application of recent challenge assays in lymphocytes which can provide measurements of individuals’ DRC, and on the latest data for more precise disease prevention and intervention. •Functional and quantitative determinations of individual’s DNA repair capacity.•From population- towards individual-based health risk assessments.•Disease prevention and intervention strategies.