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Two types of hybrids between cells with erythroid phenotype (Friend cells) and teratocarcinoma cells can be distinguished: cell hybrids with an erythroid phenotype, which release or can be induced to release large amounts of Friend spleen focus-forming virus (F-SFFV) on exposure to bromodeoxyuridine and cell hybrids with a teratocarcinoma phenotype, which do not release Friend virus and are not inducible for F-SFFV release. In this paper, we attempted to relate these differences to the expression of F-SFFV and Friend murine leukemia virus (F-MuLV) functions. Teratocarcinoma phenotype hybrids retained F-SFFV-and F-MuLV-related provirus sequences. They did not express F-SFFV- or F-MuLV-related RNA or proteins. The hybrids differentiated to endoderm-like cells on exposure to retinoic acid or hexamethylene-bis -acetamide. These cells, in contrast to the teratocarcinoma phenotype (uninduced) cells expressing SSEA-1-like antigens, did not express SSEA-1-like antigens; they formed typical, prekeratin-staining cytoskeletal structures and could be induced to release mouse interferon. The differentiating cells, but not the uninduced teratocarcinoma hybrids, were infected productively with F-MuLV or the F-MuLV--F-SFFV complex. They, however, did not express endogenous F-SFFV. Endogenous F-SFFV functions could not be rescued by infection with F-MuLV. Induction of teratocarcinoma hybrids with retinoic acid did not activate endogenous F-MuLV or F-SFFV transcription or protein synthesis. These data demonstrated two control mechanisms of Friend virus repression: one which acted trans during formation of the cell hybrids and was maintained only in teratocarcinoma phenotype cells and the other which acted cis and was still operative during induction of endodermal differentiation.

Differentiated rat thyroid epithelial cells, infected in vitro with a temperature-sensitive mutant of the Kirsten murine sarcoma virus, expressed at the permissive temperature (33 degrees C) some phenotypic properties typical of transformed cells, including morphological features, colony formation in agar, and induction of tumors in newborn animals. Specific functional markers of these differentiated cells, i.e., synthesis/secretion of thyroglobulin, synthesis of thyroglobulin mRNA and iodide uptake, were blocked during growth at 33 degrees C. Normal morphology, failure to grow in agar, and the requirement of hormones for optimal growth were all restored after shifting to the temperature nonpermissive for transformation (39 degrees C), though the typical differentiated functions remained blocked. Infection with a leukemia helper virus clone (Moloney or Kirsten murine leukemia virus) did not lead to the loss of the differentiated phenotype of rat epithelial thyroid cells, thus demonstrating that the loss of the differentiated phenotype is caused by the sarcoma virus component. These results indicate that the expression of some of the phenotypic properties of transformed differentiated rat thyroid epithelial cells is under the direct control of the p21 thermosensitive activity, whereas the block in the expression of two typical differentiation markers of thyroid epithelial cells is irreversible and probably controlled by different mechanisms.

To evaluate relationships between c-fos proto-oncogene expression and specific lineages of hematopoietic differentiation we analyzed the constitutive and TPA-induced expression of the c-fos gene in a wide variety of fresh human leukemic cells. High constitutive c-fos expression was detected in acute leukemias with monocytic phenotype (FAB M4/M5) and in subsets of B lymphoid leukemias, some of which coexpressed B lymphocytic and monocytic markers. Conversely, low basal levels of c-fos transcripts were found in pure acute granulocytic leukemias (FAB M1/M2/M3), in erythroleukemias (FAB M6), in the great majority of B, and in all T lymphoid leukemias. TPA-induced c-fos expression seems to correlate with monocytoid differentiation only when sustained levels of transcripts (ie, detectable for at least 24 hours) were detected. Sustained c-fos expression was in fact observed only in those myeloid or lymphoid cells that acquired a stable monocyte-like phenotype in response to the phorbol ester. These results indicate that high constitutive c-fos expression may identify myelomonocytic-oriented forms of leukemia, specific subsets of B lymphoid malignancies, and at least some cells terminally differentiated in vitro to a monocyte-like phenotype. c-fos oncogene expression can therefore be regarded as an additional marker for the subclassification of human leukemias.

A number of parameters were measured in a series of 12 hybrid cell clones from Chinese hamster and mouse cells to test the hypothesis that asymmetrical chromosome loss may result from asynchrony in the replication of the two parental sets of chromosomes. All clones tended to lose telocentric (mouse) chromosomes with culture time, irrespective of the starting ratio of parental chromosomes, and in all clones, biarmed (hamster) chromosomes appeared to complete DNA replication slightly earlier than telocentrics. However, no quantitative correlation could be established between the degree of asynchrony in chromosome DNA replication and the extent of chromosome loss. It appeared that telocentric chromosomes were lost more readily from those clones which started with a high hamster-to-mouse chromosome ratio.

Familial adenomatous polyposis (FAP) is known to be associated with neoplasia of various tissues, including thyroid carcinoma. Germline mutations of the tumour-suppressor gene APC, responsible for the predisposition to FAP, may therefore be involved in the pathogenesis of these tumours. In this report the structure of the APC gene has been investigated in 26 thyroid tumours, at different stages of dedifferentiation, that were surgically excised from patients with a negative history of FAP. Approximately 35% of the APC gene coding region, where most of the mutations are clustered, has been analysed by a combination of single-strand conformation polymorphism and direct sequencing. No significant alterations could be demonstrated in any sample examined. It is concluded that, at least in patients not affected by FAP, APC gene abnormalities do not seem to play a relevant role in the pathogenesis of thyroid carcinoma.