|Title:||Acrolein contributes to urothelial carcinomas in patients with chronic kidney disease||Authors:||JIAN-HUA HONG
Lee, Priscilla Ann Hweek
|Issue Date:||2020||Publisher:||Elsevier Inc.||Journal Volume:||38||Journal Issue:||5||Start page/Pages:||465-475||Source:||Urologic Oncology: Seminars and Original Investigations||Abstract:||
Background: Urothelial carcinomas (UCs) are highly prevalent in patients with end-stage renal disease. Chronic kidney disease (CKD) is the predecessor of end-stage renal disease, and it is also associated with UC. However, the interplay between CKD and UC lacks solid evidence. Acrolein is produced by polyamines and has been suggested to be the uremic “toxin.” The level of acrolein correlates well with chronic renal failure. We recently found that acrolein-induced DNA damage and inhibited DNA repair in urothelial cells, which contribute to bladder cancer. Therefore, we hypothesize that acrolein is involved in the formation of UC in patients with CKD. Materials and methods: A total of 62 UC patients and 43 healthy control subjects were recruited. Acrolein-DNA (Acr-dG) adducts and p53 gene mutations in UC tissues, plasma acrolein-protein conjugates (Acr-PC) and S-(3-hydroxypropyl)-N-acetylcysteine levels, and urinary Acr metabolites were analyzed in these patients. Results: Acr-dG levels were statistically correlated with CKD stages in UC patients (P < 0.01). Most p53 mutations were G to A and G to T mutations in these patients, and 50% of mutations at G:C pairs occurred in CpG sites, which is similar to the mutational spectra induced by Acr-dG adducts. Acr-PC levels in the plasma of UC patients with CKD were significantly higher than those of control subjects (P < 0.001). Altered urinary S-(3-hydroxypropyl)-N-acetylcysteine was also found in UC patients with CKD compared to control subjects (P < 0.005). Conclusion: These results indicate that acrolein acts as an endogenous uremic toxin and contributes to UC formation in patients with CKD. ? 2020 Elsevier Inc.
|ISSN:||1078-1439||DOI:||10.1016/j.urolonc.2020.02.017||SDG/Keyword:||(3 hydroxypropyl) n acetylcysteine; acetylcysteine; acrolein; DNA; protein p53; unclassified drug; acrolein; aged; Article; blood level; cancer patient; cancer tissue; chronic kidney failure; controlled study; DNA adduct; DNA damage; DNA repair; female; gene mutation; human; human tissue; major clinical study; male; metabolite; priority journal; transitional cell carcinoma; urine level; chronic kidney failure; complication; DNA damage; drug effect; genetics; middle aged; mutation; transitional cell carcinoma; tumor cell culture; tumor suppressor gene; urinary tract tumor; Acrolein; Aged; Carcinoma, Transitional Cell; DNA Damage; Female; Genes, p53; Humans; Male; Middle Aged; Mutation; Renal Insufficiency, Chronic; Tumor Cells, Cultured; Urologic Neoplasms
|Appears in Collections:||醫學系|
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.