Progression of two of the three transplantable Morris renal tumors: study of histology, ultrastructure and chromosome banding patterns

Abstract

The light microscopy, ultrastructure and the C- and G-banding patterns of chromosomes were studied in the latest transplant generations of Morris kidney tumours MK1, MK2, and MK3 induced in rats by 4′-fluoro-4-biphenyl-acetamide. The histopathologic appearance and the growth rate of MK1 has remained virtually unchanged through its transplantation history. Ultrastructurally, two types of neoplastic cells could be distinguished in the tumor: “dark” cells and “light” cells. The presence of light cells was not noted in an earlier ultrastructural analysis. MK1 did not show any evidence of obvious tumor progression, the two types of cells probably represent only modulation of one basic cell type. In the eleventh transfer generation of MK2 atypical fibroblasts overgrew the epithelial elements and the renal adenocarcinoma eventually progressed to fibrosarcoma. Sarcomatous transformation of the tumor was associated with a marked increase in growth rate. Under the electron microscope, the tumor was seen to be composed of fibroblast-like cells and undifferentiated elements. The atypical fibroblasts were closely associated with collagen fibers. The histologic pattern of MK3 abruptly changed in the thirteenth transplant generation. The well-differentiated adenocarcinoma progressed to anaplastic carcinoma. Ultrastructural examination revealed the emergence of new, so far undetected, undifferentiated cell types. The chromosomal constitution of these 3 transplantable kidney tumors was highly deviated from the normal rat complement. A rather homogeneous cell population was found in MK1. This slow growing tumor was hypodiploid, with a dominant stemline of 39–40 chromosomes. The chromosome complement had 14 abnormal elements in which the origin was traceable in eight. Most metaphases in MK2 were found in the hypertriploid region (67–69), 19±2 chromosomes had an abnormal banded pattern. A few large rearranged chromosomes showed constant cell to cell variation. This variable marker was most frequently the acrocentric, mar16, occasionally an isochromosome of #1, and/or a big submetacentric chromosome. In most instances, chromosomes #1, 2 and 3 were involved in these large markers. The moderately fast growing MK3 was highly heterogeneous cytogenetically and was composed exclusively of variant cells. The multiplicity of ultrastructural cell types was reflected in the wide distribution of chromosome counts. From the heterogeneous cell population 2 types of variant cells could be distinguished: (1) variant cell A with 46–60 (42%) chromosomes, many of which were abnormal, (2) variant cell B containing mainly normal chromosomes in the 5–6n region and a few markers (11%). Half of the chromosome complement in variant cell A was abnormal; the large acrocentric rearranged chromosomes were very unstable; however, the small meta-, and submetacentric markers showed a rather constant pattern. A small submetacentric marker, mar17, was present in variant cells A and B, as well as in the metaphases of MK2. The present study suggests that in the course of tumor progression the undifferentiated stem cells are called upon to insure the survival of the neoplastic cell population.