Endogenously generated DNA nucleobase modifications source, and significance as possible biomarkers of malignant transformation risk, and role in anticancer therapy

Biochim Biophys Acta Rev Cancer. 2018 Jan;1869(1):29-41. doi: 10.1016/j.bbcan.2017.11.002. Epub 2017 Nov 10.


The DNA of all living cells undergoes continuous structural and chemical alteration, which may be derived from exogenous sources, or endogenous, metabolic pathways, such as cellular respiration, replication and DNA demethylation. It has been estimated that approximately 70,000 DNA lesions may be generated per day in a single cell, and this has been linked to a wide variety of diseases, including cancer. However, it is puzzling why potentially mutagenic DNA modifications, occurring at a similar level in different organs/tissue, may lead to organ/tissue specific cancers, or indeed non-malignant disease - what is the basis for this differential response? We suggest that it is perhaps the precise location of damage, within the genome, that is a key factor. Finally, we draw attention to the requirement for reliable methods for identification and quantification of DNA adducts/modifications, and stress the need for these assays to be fully validated. Once these prerequisites are satisfied, measurement of DNA modifications may be helpful as a clinical parameter for treatment monitoring, risk group identification and development of prevention strategies.

Keywords: 5-Carboxycytosine; 5-Formylcytosine; 5-Hydroxymethylcytosine; 5-Hydroxymethyluracil; 8-Oxo-7,8-dihydroguanine; Biomarkers; Cancer; DNA damage; DNA repair; Methylation; Oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor* / genetics
  • Biomarkers, Tumor* / metabolism
  • Cell Transformation, Neoplastic* / drug effects
  • Cell Transformation, Neoplastic* / genetics
  • Cell Transformation, Neoplastic* / metabolism
  • DNA / metabolism*
  • DNA Damage / drug effects
  • DNA Damage / genetics
  • DNA Repair / drug effects
  • DNA Repair / genetics
  • Genetic Predisposition to Disease
  • Humans
  • Mutagenesis / drug effects
  • Mutagenesis / genetics*
  • Neoplasms / genetics
  • Neoplasms / pathology
  • Neoplasms / therapy*
  • Risk Factors


  • Antineoplastic Agents
  • Biomarkers, Tumor
  • DNA