A DNA adductome analysis revealed a reduction in the global level of C5-hydroxymethyl-2′-deoxycytidine in the non-tumoral upper urinary tract mucosa of urothelial carcinoma patients
Abstract Background DNA adducts, covalent modifications to DNA due to exposure to specific carcinogens, cause the mispairing of DNA bases, which ultimately results in DNA mutations. DNA methylation in the promoter region, another type of DNA base modification, alters the DNA transcription process, a...
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BMC
2021-12-01
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| Series: | Genes and Environment |
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| Online Access: | https://doi.org/10.1186/s41021-021-00228-9 |
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| author | Yuto Matsushita Yuji Iwashita Shunsuke Ohtsuka Ippei Ohnishi Takashi Yamashita Hideaki Miyake Haruhiko Sugimura |
| author_facet | Yuto Matsushita Yuji Iwashita Shunsuke Ohtsuka Ippei Ohnishi Takashi Yamashita Hideaki Miyake Haruhiko Sugimura |
| author_sort | Yuto Matsushita |
| collection | DOAJ |
| description | Abstract Background DNA adducts, covalent modifications to DNA due to exposure to specific carcinogens, cause the mispairing of DNA bases, which ultimately results in DNA mutations. DNA methylation in the promoter region, another type of DNA base modification, alters the DNA transcription process, and has been implicated in carcinogenesis in humans due to the down-regulation of tumor suppressor genes. Difficulties are associated with demonstrating the existence of DNA adducts or chemically modified bases in the human urological system. Apart from aristolochic acid-DNA adducts, which cause urothelial carcinoma and endemic nephropathy in a particular geographical area (Balkan), limited information is currently available on DNA adduct profiles in renal cell carcinoma and upper urinary tract urothelial carcinoma, including renal pelvic cancer and ureteral cancer. Method To elucidate the significance of DNA adducts in carcinogenesis in the urothelial system, we investigated 53 DNA adducts in the non-tumoral renal parenchyma and non-tumoral renal pelvis of patients with renal cell carcinoma, upper urinary tract urothelial carcinoma, and other diseases using liquid chromatography coupled with tandem mass spectrometry. A comparative analysis of tissue types, the status of malignancy, and clinical characteristics, including lifestyle factors, was performed. Results C5-Methyl-2′-deoxycytidine, C5-hydroxymethyl-2′-deoxycytidine (5hmdC), C5-formyl-2′-deoxycytidine, 2′-deoxyinosine, C8-oxo-2′-deoxyadenosine, and C8-oxo-2′-deoxyguanosine (8-OHdG) were detected in the renal parenchyma and renal pelvis. 8-OHdG was more frequently detected in the renal pelvis than in the renal cortex and medulla (p = 0.048 and p = 0.038, respectively). 5hmdC levels were significantly lower in the renal pelvis of urothelial carcinoma patients (n = 10) than in the urothelium of patients without urothelial carcinoma (n = 15) (p = 0.010). Regarding 5hmdC levels in the renal cortex and medulla, Spearman’s rank correlation test revealed a negative correlation between age and 5hmdC levels (r = − 0.46, p = 0.018 and r = − 0.45, p = 0.042, respectively). Conclusions The present results revealed a reduction of 5hmdC levels in the non-tumoral urinary tract mucosa of patients with upper urinary tract urothelial carcinoma. Therefore, the urothelial cell epithelia of patients with upper urinary tract cancer, even in non-cancerous areas, may be predisposed to urothelial cancer. |
| first_indexed | 2024-12-14T07:37:34Z |
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| spelling | doaj.art-fb0898992ccc409bba965536dc3ca1d42022-12-21T23:11:09ZengBMCGenes and Environment1880-70622021-12-0143111410.1186/s41021-021-00228-9A DNA adductome analysis revealed a reduction in the global level of C5-hydroxymethyl-2′-deoxycytidine in the non-tumoral upper urinary tract mucosa of urothelial carcinoma patientsYuto Matsushita0Yuji Iwashita1Shunsuke Ohtsuka2Ippei Ohnishi3Takashi Yamashita4Hideaki Miyake5Haruhiko Sugimura6Department of Tumor Pathology, Hamamatsu University School of MedicineDepartment of Tumor Pathology, Hamamatsu University School of MedicineDepartment of Tumor Pathology, Hamamatsu University School of MedicineDepartment of Tumor Pathology, Hamamatsu University School of MedicineDepartment of Tumor Pathology, Hamamatsu University School of MedicineDepartment of Urology, Hamamatsu University School of MedicineDepartment of Tumor Pathology, Hamamatsu University School of MedicineAbstract Background DNA adducts, covalent modifications to DNA due to exposure to specific carcinogens, cause the mispairing of DNA bases, which ultimately results in DNA mutations. DNA methylation in the promoter region, another type of DNA base modification, alters the DNA transcription process, and has been implicated in carcinogenesis in humans due to the down-regulation of tumor suppressor genes. Difficulties are associated with demonstrating the existence of DNA adducts or chemically modified bases in the human urological system. Apart from aristolochic acid-DNA adducts, which cause urothelial carcinoma and endemic nephropathy in a particular geographical area (Balkan), limited information is currently available on DNA adduct profiles in renal cell carcinoma and upper urinary tract urothelial carcinoma, including renal pelvic cancer and ureteral cancer. Method To elucidate the significance of DNA adducts in carcinogenesis in the urothelial system, we investigated 53 DNA adducts in the non-tumoral renal parenchyma and non-tumoral renal pelvis of patients with renal cell carcinoma, upper urinary tract urothelial carcinoma, and other diseases using liquid chromatography coupled with tandem mass spectrometry. A comparative analysis of tissue types, the status of malignancy, and clinical characteristics, including lifestyle factors, was performed. Results C5-Methyl-2′-deoxycytidine, C5-hydroxymethyl-2′-deoxycytidine (5hmdC), C5-formyl-2′-deoxycytidine, 2′-deoxyinosine, C8-oxo-2′-deoxyadenosine, and C8-oxo-2′-deoxyguanosine (8-OHdG) were detected in the renal parenchyma and renal pelvis. 8-OHdG was more frequently detected in the renal pelvis than in the renal cortex and medulla (p = 0.048 and p = 0.038, respectively). 5hmdC levels were significantly lower in the renal pelvis of urothelial carcinoma patients (n = 10) than in the urothelium of patients without urothelial carcinoma (n = 15) (p = 0.010). Regarding 5hmdC levels in the renal cortex and medulla, Spearman’s rank correlation test revealed a negative correlation between age and 5hmdC levels (r = − 0.46, p = 0.018 and r = − 0.45, p = 0.042, respectively). Conclusions The present results revealed a reduction of 5hmdC levels in the non-tumoral urinary tract mucosa of patients with upper urinary tract urothelial carcinoma. Therefore, the urothelial cell epithelia of patients with upper urinary tract cancer, even in non-cancerous areas, may be predisposed to urothelial cancer.https://doi.org/10.1186/s41021-021-00228-9DNA adductDNA adductomeDNA adductomicsC5-hydroxymethyl-2′-deoxycytidineRenal cell carcinomaUpper urinary tract urothelial carcinoma |
| spellingShingle | Yuto Matsushita Yuji Iwashita Shunsuke Ohtsuka Ippei Ohnishi Takashi Yamashita Hideaki Miyake Haruhiko Sugimura A DNA adductome analysis revealed a reduction in the global level of C5-hydroxymethyl-2′-deoxycytidine in the non-tumoral upper urinary tract mucosa of urothelial carcinoma patients Genes and Environment DNA adduct DNA adductome DNA adductomics C5-hydroxymethyl-2′-deoxycytidine Renal cell carcinoma Upper urinary tract urothelial carcinoma |
| title | A DNA adductome analysis revealed a reduction in the global level of C5-hydroxymethyl-2′-deoxycytidine in the non-tumoral upper urinary tract mucosa of urothelial carcinoma patients |
| title_full | A DNA adductome analysis revealed a reduction in the global level of C5-hydroxymethyl-2′-deoxycytidine in the non-tumoral upper urinary tract mucosa of urothelial carcinoma patients |
| title_fullStr | A DNA adductome analysis revealed a reduction in the global level of C5-hydroxymethyl-2′-deoxycytidine in the non-tumoral upper urinary tract mucosa of urothelial carcinoma patients |
| title_full_unstemmed | A DNA adductome analysis revealed a reduction in the global level of C5-hydroxymethyl-2′-deoxycytidine in the non-tumoral upper urinary tract mucosa of urothelial carcinoma patients |
| title_short | A DNA adductome analysis revealed a reduction in the global level of C5-hydroxymethyl-2′-deoxycytidine in the non-tumoral upper urinary tract mucosa of urothelial carcinoma patients |
| title_sort | dna adductome analysis revealed a reduction in the global level of c5 hydroxymethyl 2 deoxycytidine in the non tumoral upper urinary tract mucosa of urothelial carcinoma patients |
| topic | DNA adduct DNA adductome DNA adductomics C5-hydroxymethyl-2′-deoxycytidine Renal cell carcinoma Upper urinary tract urothelial carcinoma |
| url | https://doi.org/10.1186/s41021-021-00228-9 |
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