Morphologic changes in rat urothelial cells during carcinogenesis: I. Histologic and cytologic changes.

Area of Science:

• Urothelial Carcinogenesis
• Cytopathology
• Animal Models

Background:

• Developing bladder tumors in rats requires reliable cell sampling and classification methods.
• Existing techniques for image or flow cytometry need to correlate with tumor origin.

Purpose of the Study:

• To establish and validate methods for classifying exfoliated cells from developing rat bladder tumors.
• To correlate cytopathologic changes in urine with histological findings of bladder lesions.

Main Methods:

• Rats were administered N-butyl-4-N-hydroxybutylnitrosamine (BBN) carcinogen and monitored over 62 weeks.
• Bladder tissues were histologically evaluated; urine and bladder cells were Papanicolaou stained for cytopathologic analysis.
• Urine sediments were collected and analyzed for exfoliated cell changes.

Main Results:

• Histology showed hyperplasia progressing to papillary transitional cell tumors and invasive carcinoma.
• Cytology revealed reparative changes at 14-26 weeks and neoplastic changes at 45-62 weeks; both were present at 34 weeks.
• Urine samples from treated rats yielded significantly more cells (>1000) than controls (<1000), with up to 11% adequately preserved.

Conclusions:

• Urine cytology can detect neoplastic changes in a rat bladder cancer model.
• The developed methods provide a system for classifying exfoliated cells related to bladder lesions.
• This approach supports the use of exfoliated cells in urine for monitoring bladder tumor development.