1. The interaction of arsenic and N-butyl-N-(4-hydroxybutyl)nitrosamine on urothelial carcinogenesis in mice
- Author
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Shou-Chieh Wang, Lei-Chen Lin, Ching-Hsein Chen, Mohammad Mezbahul Haque, Yi-Wen Liu, Yuan-Chang Dai, and Wei-Han Lin
- Subjects
0301 basic medicine ,Male ,Carcinogenesis ,lcsh:Medicine ,medicine.disease_cause ,Pathology and Laboratory Medicine ,Biochemistry ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,NAD(P)H Dehydrogenase (Quinone) ,Medicine and Health Sciences ,Drug Interactions ,lcsh:Science ,Glutathione Transferase ,Multidisciplinary ,Urinary bladder ,DNA methylation ,Chemistry ,Animal Models ,Chromatin ,Gene Expression Regulation, Neoplastic ,Nucleic acids ,medicine.anatomical_structure ,Oncology ,Experimental Organism Systems ,030220 oncology & carcinogenesis ,Physical Sciences ,Female ,Epigenetics ,Anatomy ,DNA modification ,Chromatin modification ,Research Article ,Chemical Elements ,Chromosome biology ,Cyclin-Dependent Kinase Inhibitor p21 ,Dysplasia ,Cell biology ,Sp1 Transcription Factor ,Bladder ,Urinary Bladder ,chemistry.chemical_element ,Mouse Models ,Research and Analysis Methods ,Carcinomas ,Arsenic ,03 medical and health sciences ,Model Organisms ,Signs and Symptoms ,Diagnostic Medicine ,medicine ,Genetics ,Animals ,Urothelium ,Carcinogen ,Carcinoma, Transitional Cell ,Bladder cancer ,Arsenic toxicity ,lcsh:R ,Biology and Life Sciences ,Cancers and Neoplasms ,Renal System ,DNA ,medicine.disease ,Mice, Inbred C57BL ,030104 developmental biology ,Urinary Bladder Neoplasms ,Nitrosamine ,Cancer research ,Carcinogens ,lcsh:Q ,Butylhydroxybutylnitrosamine ,Gene expression ,Carrier Proteins - Abstract
The bladder is an important organ for the storage of excreted water and metabolites. If metabolites with carcinogenic characteristics are present in urine, the urothelial lining of the bladder could be damaged and genetically altered. In this study, we analyzed the interaction of arsenic and N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) on mouse bladder carcinogenesis. Our previous study found that arsenic affects BBN-altered urothelial enzymatic activity, protein expression, DNA oxidation and global DNA CpG methylation levels. In this study, two mouse models were used. First, after administering a co-treatment of BBN and arsenic for 20 weeks, BBN alone led to a urothelial carcinoma formation of 20%, and arsenic promoted a BBN-induced urothelial carcinoma formation of 10%. The protein expression of GSTM1, GSTO1, NQO1, and p21 did not change by arsenic along with the BBN co-treatment, but the Sp1 expression increased. In the second mouse model, BBN was a pretreatment promoter; arsenic dose-dependently deteriorated BBN-promoted dysplasia by 10% and 40% at 10 ppm and 100 ppm, respectively. Conversely, BBN pretreatment also accelerated arsenic-induced dysplasia by 30%. The urothelial carcinogenic effect reversed after ceasing BBN for a period of 20 weeks. In summary, three conclusions were drawn from this study. The first is the mutual promotion of arsenic and BBN in bladder carcinogenesis. Second, arsenic dosages without bladder carcinogenicity (10 ppm) or with slight carcinogenicity (100 ppm) promote BBN-induced mice bladder cancer progression. Finally, the dysplastic urothelium had reverted to near-normal morphology after ceasing BBN intake for 20 weeks, providing a good suggestion for people who want to quit smoking.
- Published
- 2017