Significant overexpression of metallothionein and cyclin D1 and apoptosis in the early process of rat urinary bladder carcinogenesis induced by treatment with N-butyl-N-(4-hydroxybutyl)nitrosamine or sodium L-ascorbate.

摘要: Effects of a genotoxic bladder carcinogen, N-butyl-N-(4hydroxybutyl)nitrosamine (BBN) and non-genotoxic promoter, sodium L-ascorbate (Na-AsA), on protein expression, cell proliferation apoptosis the epithelium with or without influence testicular castration were investigated. Male F344 rats divided into six groups (groups 1‐6). BBN was given 0.05% drinking water to 1 4 for 8 weeks, 2 5 received diet 5% Na-AsA. Then animals treated any chemicals. Groups 3 6 non-treated controls. Testicular carried out weeks before commencement chemical treatment 4‐6. The total observation period 18 weeks. Overexpression cyclin D1 induced by but not Na-AsA degree overexpression higher in order simple hyperplasia, papillary nodular papilloma carcinoma. Metallothionein (MT) also overexpressed Na-AsA, decreased papillomas never found Cyclin D1-positive cells essentially MT-negative. Therefore, it is speculated that MT protects genes from insult carcinogens its lack associated tumor development. Apoptotic death occurred during after their withdrawal. Chromatin condensation many G 0/G1 particularly marked flow cytometry analysis week cessation treatment, this being considered as an early apoptotic change. Although had no above events, resulted formation compared case similarly intact animals. Our data demonstrate specific suggest may play important suppressive role stages rat urinary carcinogenesis.