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.
C5-hydroxymethyl-2′-deoxycytidine
DNA adduct
DNA adductome
DNA adductomics
Oxidative DNA damage
Renal cell carcinoma
Upper urinary tract urothelial carcinoma
Journal
Genes and environment : the official journal of the Japanese Environmental Mutagen Society
ISSN: 1880-7046
Titre abrégé: Genes Environ
Pays: England
ID NLM: 101285347
Informations de publication
Date de publication:
02 Dec 2021
02 Dec 2021
Historique:
received:
15
09
2021
accepted:
11
11
2021
entrez:
2
12
2021
pubmed:
3
12
2021
medline:
3
12
2021
Statut:
epublish
Résumé
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. 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. 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). 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.
Sections du résumé
BACKGROUND
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
METHODS
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
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
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.
Identifiants
pubmed: 34852853
doi: 10.1186/s41021-021-00228-9
pii: 10.1186/s41021-021-00228-9
pmc: PMC8638144
doi:
Types de publication
Journal Article
Langues
eng
Pagination
52Subventions
Organisme : Japan Society for the Promotion of Science
ID : JP22659072
Organisme : Japan Society for the Promotion of Science
ID : JP24659161
Organisme : Japan Society for the Promotion of Science
ID : JP26670187
Organisme : Japan Society for the Promotion of Science
ID : JP16K15256
Organisme : Japan Agency for Medical Research and Development
ID : JP20ck0106545
Organisme : Japan Agency for Medical Research and Development
ID : JP19ck0106264
Organisme : Hamamatsu University School of Medicine
ID : HUSM Grant-in-Aid
Informations de copyright
© 2021. The Author(s).
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