Micronuclei Formation upon Radioiodine Therapy for Well-Differentiated Thyroid Cancer: The Influence of DNA Repair Genes Variants

Santos, Luís S.; O, Gil; Silva, Susana N.; Gomes, Bruno Costa; Ferreira, Teresa; Limbert, Edward; Rueff, José

doi:10.3390/genes11091083

Cited by 8 publications

(5 citation statements)

References 126 publications

(266 reference statements)

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“…DNA damage can activate DNA damage checkpoints, which can slow down or arrest cell cycle progression, so that cells can repair or prevent the spread of damaged chromosomes [ 33 , 34 ]. If the DNA damage can be repaired, the cells return to a normal cell cycle and survive, or otherwise they will lead to further chromosomal damage [ 35 ], and eventually lead to cell death [ 36 ]. Nicotine can inhibit these toxic effects of NNK by inhibiting CYP2A13.…”

Section: Resultsmentioning

confidence: 99%

Nicotine Inhibits the Cytotoxicity and Genotoxicity of NNK Mediated by CYP2A13 in BEAS-2B Cells

et al. 2022

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Both tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and nicotine can be metabolized by cytochrome P450 2A13 (CYP2A13). Previous studies have shown that nicotine has a potential inhibitory effect on the toxicity of NNK. However, due to the lack of CYP2A13 activity in conventional lung cell lines, there had been no systematic in vitro investigation for the key target organ, the lung. Here, BEAS-2B cells stably expressing CYP2A13 (B-2A13 cells) were constructed to investigate the effects of nicotine on the cytotoxicity and genotoxicity of NNK. The results showed more sensitivity for NNK-induced cytotoxicity in B-2A13 cells than in BEAS-2B and B-vector cells. NNK significantly induced DNA damage, cell cycle arrest, and chromosomal damage in B-2A13 cells, but had no significant effect on BEAS-2B cells and the vector control cells. The combination of different concentration gradient of nicotine without cytotoxic effects and a single concentration of NNK reduced or even counteracted the cytotoxicity and multi-dimensional genotoxicity in a dose-dependent manner. In conclusion, CYP2A13 caused the cytotoxicity and genotoxicity of NNK in BEAS-2B cells, and the addition of nicotine could inhibit the toxicity of NNK.

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Section: Resultsmentioning

confidence: 99%

Nicotine Inhibits the Cytotoxicity and Genotoxicity of NNK Mediated by CYP2A13 in BEAS-2B Cells

et al. 2022

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“…The distinction between the influence of LS on thyroid cancer or MMR/MSI anomalies in subjects with TC is mandatory. However, the current level of understanding is based on isolated studies [37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54]. TC, the most frequent endocrine cancer, is associated with increasing incidence, and some particular forms have high genetic susceptibility [38].…”

Section: Tc and Mmr/msi Involvementmentioning

confidence: 99%

“…Of course, the epidemiologic impact of the two malignancies is distinct, and this might explain why limited data are published on ACC versus TCs. The assessment of MMR/MSI seems to add an interesting and valuable piece to this challenging puzzle of these endocrine cancers [42,48,53,54].…”

Section: Tc and Mmr/msi Involvementmentioning

confidence: 99%

Pathogenic Insights into DNA Mismatch Repair (MMR) Genes–Proteins and Microsatellite Instability: Focus on Adrenocortical Carcinoma and Beyond

Cârșote

Turturea

Turturea³

et al. 2023

Diagnostics

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DNA damage repair pathways, including mismatch repair (MMR) genes, are prone to carcinoma development in certain patients. The assessment of the MMR system is widely recognized as part of strategies concerning solid tumors (defective MMR cancers), especially MMR proteins (through immunohistochemistry), and molecular assays for microsatellite instability (MSI). We aim to highlight the status of MMR genes–proteins (including MSI) in the relationship with ACC (adrenocortical carcinoma) according to current knowledge. This is a narrative review. We included PubMed-accessed, full-length English papers published between January 2012 and March 2023. We searched studies on ACC patients for whom MMR status was assessed, respectively subjects harboring MMR germline mutations, namely Lynch syndrome (LS), who were diagnosed with ACC. MMR system assessments in ACCs involve a low level of statistical evidence. Generally, there are two main types of endocrine insights: 1. the role of MMR status as a prognostic marker in different endocrine malignancies (including ACC)—which is the topic of the present work, and 2. establishing the indication of immune checkpoint inhibitors (ICPIs) in selective, mostly highly aggressive, non-responsive to standard care forms upon MMR evaluation (which belongs to the larger chapter of immunotherapy in ACCs). Our one-decade, sample-case study (which, to our knowledge, it is the most comprehensive of its kind) identified 11 original articles (from 1 patient to 634 subjects per study diagnosed with either ACC or LS). We identified four studies published in 2013 and 2020 and two in 2021, three cohorts and two retrospective studies (the publication from 2013 includes a retrospective and a cohort distinct section). Among these four studies, patients already confirmed to have LS (N = 643, respective 135) were found to be associated with ACC (N = 3, respective 2), resulting in a prevalence of 0.0046%, with a respective of 1.4% being confirmed (despite not having a large amount of similar data outside these two studies). Studies on ACC patients (N = 364, respective 36 pediatric individuals, and 94 subjects with ACC) showed that 13.7% had different MMR gene anomalies, with a respective of 8.57% (non-germline mutations), while 3.2% had MMR germline mutations (N = 3/94 cases). Two case series included one family, with a respective four persons with LS, and each article introduced one case with LS-ACC. Another five case reports (between 2018 and 2021) revealed an additional five subjects (one case per paper) diagnosed with LS and ACC (female to male ratio of 4 to 1; aged between 44 and 68). Interesting genetic testing involved children with TP53-positive ACC and further MMR anomalies or an MSH2 gene-positive subject with LS with a concurrent germline RET mutation. The first report of LS-ACC referred for PD-1 blockade was published in 2018. Nevertheless, the use of ICPI in ACCs (as similarly seen in metastatic pheochromocytoma) is still limited. Pan-cancer and multi-omics analysis in adults with ACC, in order to classify the candidates for immunotherapy, had heterogeneous results, and integrating an MMR system in this larger and challenging picture is still an open issue. Whether individuals diagnosed with LS should undergo surveillance for ACC has not yet been proven. An assessment of tumor-related MMR/MSI status in ACC might be helpful. Further algorithms for diagnostics and therapy, also taking into consideration innovative biomarkers as MMR-MSI, are necessary.

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“…Therefore, it is expected that a relationship between SNPs and gene expression exists. SNPs in DNA repair genes for HR and MMR pathways involved in repairing IR-induced DNA damage are significantly associated with DNA damage in the form of micronuclei formation in patients treated with radioiodine therapy [ 107 ]. Correlation analyses of SNPs in the BER pathway with DNA damage, DNA repair, and mRNA expression in healthy donors also supported a relationship between BER gene polymorphisms and individual radiosensitivity [ 108 ].…”

Section: Genomic Alterations In Human Cells Cultured In Simulated Space Conditionsmentioning

confidence: 99%

Genomic Changes Driven by Radiation-Induced DNA Damage and Microgravity in Human Cells

Beheshti

McDonald

Hada

et al. 2021

IJMS

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The space environment consists of a complex mixture of different types of ionizing radiation and altered gravity that represents a threat to humans during space missions. In particular, individual radiation sensitivity is strictly related to the risk of space radiation carcinogenesis. Therefore, in view of future missions to the Moon and Mars, there is an urgent need to estimate as accurately as possible the individual risk from space exposure to improve the safety of space exploration. In this review, we survey the combined effects from the two main physical components of the space environment, ionizing radiation and microgravity, to alter the genetics and epigenetics of human cells, considering both real and simulated space conditions. Data collected from studies on human cells are discussed for their potential use to estimate individual radiation carcinogenesis risk from space exposure.

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Micronuclei Formation upon Radioiodine Therapy for Well-Differentiated Thyroid Cancer: The Influence of DNA Repair Genes Variants

Cited by 8 publications

References 126 publications

Nicotine Inhibits the Cytotoxicity and Genotoxicity of NNK Mediated by CYP2A13 in BEAS-2B Cells

Nicotine Inhibits the Cytotoxicity and Genotoxicity of NNK Mediated by CYP2A13 in BEAS-2B Cells

Pathogenic Insights into DNA Mismatch Repair (MMR) Genes–Proteins and Microsatellite Instability: Focus on Adrenocortical Carcinoma and Beyond

Genomic Changes Driven by Radiation-Induced DNA Damage and Microgravity in Human Cells

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