DNA repair phenotype and cancer susceptibility—A mini review

Abstract

DNA repair is a complicated biological process, consisting of several distinct pathways, that plays a fundamental role in the maintenance of genomic integrity. The very important field of DNA repair and cancer risk has developed rapidly in the past decades. In this review of selected published data from our laboratory, we describe mostly our work on the study of phenotypic markers of nucleotide excision repair (NER), as measured by the benzo(a)pyrene diol epoxide (BPDE)/ultraviolet (UV)-induced mutagen sensitivity assays, BPDE-induced adduct assay, host cell reactivation (HCR)-DNA repair capacity (DRC) assay, reverse transcription-polymerase chain reaction (RT-PCR) assay and reverse-phase protein lysate microarray (RPP) assay, by using peripheral blood lymphocytes in a series of molecular epidemiological studies. Results of our studies suggest that individuals with reduced DRC have an elevated cancer risk. This finding needs additional validation by other investigators, and we also discussed issues in conducting this kind of research in the future.

Multiplexed DNA repair assays for multiple lesions and multiple doses via transcription inhibition and transcriptional mutagenesis

“…These methods do not require the generation of cell lysates or the use of in vitro assays and can measure in vivo DRC at multiple doses or in multiple repair pathways simultaneously. As a result, these assays outperform current methods of measuring DRC (20,27) and have the potential to be used to personalize the prevention and treatment of cancer and other diseases caused by inefficient repair of DNA damage.…”

“…Host cell reactivation (HCR) assays report the ability of cells to repair DNA damage that blocks transcription of a transiently transfected reporter gene (8,9,(25)(26)(27)(28). Repair of the transcription-blocking lesion reactivates reporter gene expression, thus providing a quantitative readout for DRC.…”

Genetic Variants of NBS1 Predict Clinical Outcome of Platinum-based Chemotherapy in Advanced Non-small Cell Lung Cancer in Chinese

“…Taken together, it seems this C variant allele is associated with decreased DNA repair activity. DNA repair has been termed a double-edged sword, with the reason that although decreased DNA repair may increase the susceptibility of cancer, it might also simultaneously improve survival in patients already diagnosed with cancer, when treated with agents inducing DNA damage like cisplatin or carboplatin (Li et al, 2009;Wang et al, 2011).…”

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“…These predisposing factors of BCC were reviewed by Dessinioti et al, 2010. Individuals with lower DNA repair capacity may be more vulnerable. Lower DNA repair capacity was measured in a UV-based host-cell reactivation assay in individuals with basal cell carcinoma and cutaneous melanoma (Li et al, 2009). Several studies have reported an age-associated decline in NER and BER (Moriwaki and Takahashi, 2008), which could result in an accumulation of damage.…”