Long-term serial transplantation of different human bladder carcinomas into NMRI nu/nu mice. Histologic, flow cytometric and growth studies.

Sixteen human bladder carcinomas (BCs) were transplanted into NMRI nu/nu mice with an acceptance rate of 62.5%. Six of the 16 (37.5%) BCs were successfully retransplanted up to 14 passages. Histologic grading and traumatization during surgery influenced the acceptance rate. Grade-I tumors were rarely accepted, unless they were obtained during open surgery, rather than by transurethral resection (TUR). Specimens taken by TUR or by electric cut during open surgery were almost never accepted. Identity of the transplanted tumor tissue with the original human BCs could be demonstrated by flow cytometry and by light microscopy through several passages in all accepted tumors. However, although the tumors retained their major structural features, their proliferative activity increased, particularly that of grade-I tumors. The five tumors that were transitional-cell carcinomas and could be subpassed had three characteristics not seen before in transplanted renal cell carcinomas: tumor growth started after a delay which shortened with each further passage; growth rates of tumors only in their first passage correlated with the prognosis of the corresponding patients, and with each further passage, tumor growth accelerated until a doubling time of about 1 week was observed. From then on, tumor growth was almost identical in all five tumors. In contrast to our experience with transplanted renal cell carcinomas, flow cytometric evaluation of the transplanted and further passaged BCs revealed changes in DNA index and an increase in proliferative rate and it seems that BCs were strongly influenced by host factors.