The rat bladder tumor model system RBT resembles phenotypically and cytogenetically human superficial transitional cell carcinoma

Abstract

A cohort of 300 ACI rats was kept under standard laboratory conditions. After 30 months or upon natural death, complete autopsy was performed. In the genitourinary tract four kidney and five bladder tumors were found. Two of these bladder tumors, RBT323 and RBT157, are serially transplantable. In the fifth transplant generation the RBT323 tumor becomes metastatic to the lungs in more than 90% of animals. The metastatic ability of the RBT157 tumor changes from low to intermediate (50% of the rats have lung metastases) in the fourth passage. Histologically, the initial passages of the RBT323 and 157 tumors are grade II transitional cell carcinoma (TCC). The histological pattern of the RBT157 tumor remains essentially unchanged, whereas the RBT323 tumor progresses to a grade III tumor in the third passage. Electron microscopical studies reveal oblong elliptical and round vesicles lined by an asymmetrical unit membrane in the tumor cells, which stresses the urothelial origin of the tumors. Immunohistochemically both tumors show expression of cytokeratin 5, 7, 8 and 18. The progression of the tumors to a metastatic phenotype, however, is not associated with a specific change in the morphological characteristics. Cytogenetic analysis shows that both tumors are peridiploid with few marker chromosomes. Interestingly, both of these independently arising tumors exhibit a loss of chromosome 5. Rat chromosome 5 is syntenic to the major portion of human chromosome 9 (p23-qter). Loss of chromosome 9 is a cytogenetic trait of human superficial TCC, hence the RBT model is also in cytogenetic respect similar to human TCC.(ABSTRACT TRUNCATED AT 250 WORDS)

Characterization of a novel transplantable orthotopic rat bladder transitional cell tumour model

“…This requires an orthotopic, superficial and purely TCC model with a reasonable bladder volume and urethral caliber to introduce the laser fibre or other therapeutic agents into the bladder. Spontaneously arising rodent bladder tumours are rare (van Moorselaar et al, 1993). A suitable rat model may meet these criteria, since carcinogen induced primary bladder tumours closely parallel the human disease in both morphology and tumour biology (Oyasu, 1995).…”

Urinary System

“…The expression of intermediate filaments can also be used as a marker for progression of rat TCC. A loss of chromosome 5 was reported in two rat TCC cell lines (Van Moorselaar et al 1993). Decreased CK13 and increased CK18 expression in highly malignant rat bladder tumors was consistent with the findings in human TCe.…”

Current animal models of bladder cancer: Awareness of translatability (Review)

“…AY-27 and MBT-2 were initially induced by feeding C3H/He mouse and Fischer 344 rat strains with N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide (FANFT) (35,36), while MB49 was induced by administering 7,12-dimethylbenzanthracene to the C57BL/6 mouse strain (37). However, one type of rodent cancer cell line may not be compatible to the rodents of other strains from which the cell line was originally derived (38,39). …”