Proliferation of cultivated cells from normal, preneoplastic and neoplastic human breast tissue--preliminary report.

The success of cultivation of epithelial cells from normal, neoplastic and preneoplastic tissues is reviewed. MCDB 170 medium with special supplements is useful for epithelial cell culture. The epithelial character was demonstrated by the reaction with 3 different monoclonal antibodies. Most cell populations from preneoplastic and neoplastic tissues were identified as fibroblasts. Cell proliferation as measured by cell doubling time, labeling index, flow cytometry did not differ between the tissue types examined. Only 3H-thymidine uptake showed an increased tendency in cells from preneoplastic and neoplastic tissues. The use of normal human breast epithelial cells for molecular biological studies is recommended.

[Fine structure studies and identification of lectin receptors on the viral envelope of two HIV-isolates]. / Feinstrukturuntersuchungen und Identifizierung von Lektinrezeptoren auf der Virushülle zweier HIV-Isolate.

The electron microscopic particle findings were compared with the levels of revertase in corresponding samples over a longer period of time, and a good correlation was found. Comparative investigations of the fine-structure of two HIV isolates did not reveal any morphological differences. It can be assumed, on the basis of the comparative studies on lectin receptors using Helix pomatia lectin, that the viral envelopes of the two isolates are equipped similarly with N-acetyl-d-galactosamine. The differences are not significant with mature particles.

Suppression of human lymphocyte mitogen response by proteins of the type-D retrovirus PMFV.

A type-D retrovirus, derived from a human cell line and designated PMFV, which is related to, but distinct from the Mason-Pfizer monkey virus (MPMV) suppressed the in vitro mitogen response of human lymphocytes. PMFV was suppressive either as intact virus or after disruption by ether or detergents. In kinetic studies, the time course of the interaction between suppressive virus components and lymphocytes was characterized. Neither cytotoxicity nor time shifts in optimum 3H-thymidine incorporation of responding lymphocytes were observed. The suppressive activity of the disrupted virus was diminished by heating, freeze-thawing or treatment with pronase or trypsin, indicating temperature-sensitive proteins as suppressive components. By Sephacryl S-200 gel chromatography, molecular weights of approximately 70 and 15 kDa were determined for the suppressive components which were isolated from disrupted virus or virus-producing cells but not from non-infected cells.

[Viral carcinogenesis]. / Virale Kanzerogenese.

A short overview of the history of tumor virology is given with respect to the special data of research in this field done by Arnold Graffi and his coworkers. The theory of viral etiology of tumors during the 75 years since its inauguration had to be proven by scientists fighting for the idea of viral agents being the cause of several types of cancer in animals and man. Today this theory is accepted; a series of human tumors is known as induced by viruses, too. Moreover, tumor viruses have increased our knowledge of mechanisms of malignant transformation and the discovery of one genes has opened new possibilities for analysis of the process of cancerogenesis.

[Immunosuppression by retroviruses in tumors and immune deficiency diseases]. / Immunosuppression durch Retroviren bei Tumoren und Immundefizienzerkrankungen.

Most retroviruses are immunosuppressive in vitro and in vivo. They are able to enhance virus-induced tumor development and/or to induce acquired immune deficiency syndromes (AIDS) which are characterized by malignant tumors and opportunistic infections. Experimental evidence for the immunosuppressive properties of several type D viruses derived from human cell lines and other retroviruses is presented.

Electron microscopic investigation on the fine structure of the virus of enzootic bovine leukosis (BLV).

Systematically electron microscopical control of BLV producing cells and stimulated lymphocytes of leukotic cattle in the last years revealed maturation processes of BLV in a different form from comparable type C viruses. Electron microscopic representation of bridge-like junctions between core and envelope within examined retroviruses were discussed and compared with new model concepts.

Suppression of human lymphocyte mitogen response by retroviruses of type D. II. Non-activity of Mason-Pfizer monkey virus versus activity of human cell line derived virus PMFV.

In contrast to the human cell line derived type D retrovirus PMFV, the Mason-Pfizer monkey virus (MPMV) does not suppress the mitogen response of normal human lymphocytes. Both viruses have been propagated on the same cell lines and purified by the same methods. MPMV did not contain a factor able to abolish PMFV-induced suppression of the mitogen response. Neither could MPMV suppress the mitogen response of lymphocytes from rhesus monkeys or baboons. PMFV however inhibited their reactivity.

The possible etiological role of retroviruses in human tumors.

A short review of the data on retroviruses and human tumors from the past is given and discussed in comparison to some features of animal oncoviruses. The epidemiological association of a newly isolated retrovirus (HTLV/ATLV) with human adult T-cell lymphomas and the demonstration of onc-genes homologous to those of retroviruses in human cellular DNA has opened new aspects of the possible role of retroviruses in the etiology of human tumors.

Suppression of human lymphocyte mitogen response by disrupted primate retroviruses of type C (baboon endogenous virus) and type D (PMFV).

Disrupted primate retroviruses of type C (baboon endogenous virus, BaEV) and type D (human cell line-derived isolate PMFV) considerably suppressed Concanavalin A - induced blastogenic response of human lymphocytes. Rauscher mouse leukemia virus (RLV) displayed a suppressive activity on murine splenic lymphocytes when tested under analogous conditions. The immunosuppressive activities were shown not to result from cytotoxicity or from virus-mitogen binding.

Viruses and cancer risk in man.

The present state of tumor virus research in man is analysed in order to evaluate the cancer risk by viruses in man. For most of the viruses isolated from human tumorous or normal tissues and similar to oncogenic viruses of animals the participation as causative agent in the multifactorial process of cancer induction, promotion and realization in man is not yet established. This holds true for DNA viruses (paillomaviruses, SV 40-related viruses, Herpesvirus 2, hepatitis B virus) as well as for the retroviruses. There are, however, data which give circumstantial evidence for the association of members of these groups of viruses with certain types of human tumors. The foremost candidate as human tumor virus is the Epstein-Barr virus--an essential causative factor for Burkitt's lymphoma and nasopharyngeal carcinomas.

Common antigenic determinants on structural proteins p10--12 of PMFV and MPMV type D retroviruses.

PMFV, a type D retrovirus isolated from a malignant human embryo cell line, was compared with Mason-Pfizer monkey virus (MPMV) in a sensitive tannic acid enhanced indirect immunodiffusion test. In addition to the previously shown common antigens, both viruses contain identical group-specific antigenic determinants on their p 10--12 as demonstrated with a specific p 10--12 MPMV test system. Interspecies mammalian type C virus antigens were not detected in highly concentrated PMFV preparations.

The protein pattern of PMF virus, a type-D retrovirus from malignant permanent human cell lines.

The protein pattern of a type-D retrovirus (PMFV) isolated from and propagated in human cell lines has been investigated using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Staining with Coomassie blue and labeling with 14C-leucine/14C-lysine revealed five viral polypeptides with molecular weights of 10,000, 12,000, 15,000, 25,000, and 68,000. The 68,000 D-protein was shown to be a glycoprotein by incorporation of 3H-glucosamine and the 15,000 D-protein was identified as a phosphoprotein. By comparing PMFV with the closely related Mason-Pfizer monkey virus (MPMV) in co-electrophoresis experiments no clear difference was detected in viral 14C-leucine/14C-lysine profiles. The viruses differ, however, with respect to their glycoprotein patterns. A glycoprotein corresponding to the gp20 of MPMV has not been detected in PMFV irrespective of the cell line used for propagation of viruses.

[Isolation of foamy virus type II out of haematopoetic cells from baboons with haematoblastoses and from healthy animals (author's transl)]. / Isolierung des Foamy-Virus Typ II aus den Zellen der blutbildenden Organe von gesunden und an Hämoblastose erkrankten Mantelpavianen.

Foamy virus Type II persists in the haematopoetic organs of 75 percent of baboons in the Suchumi flock. A mixed infection with foamy virus types I and II seems to be possible. Foamy viruses are isolated as well from monkeys with haemoblastoses as from healthy animals. New information concerning the intrauterine transmission of foamy viruses were obtained.

The autoradiographic pattern of DNA synthesis in Papova virus- and N-methyl-N-nitroso urea (MNU)-induced skin tumors of the Syrian hamster (Mesocricetus auratus).

In skin tumors induced in Syrian hamsters by Papova viruses or produced chemically by dripping of methylnitroso urea (MNU) the pattern of DNA synthesis was studied in vitro and in vivo by autoradiography. The greater part of DNA synthesis in the Papova tumor of the hamster is of cellular origin. Only the cells localized adjacent to keratinizing regions of the tumors may be considered as virus-infected with progressive maultiplication of viruses. This also applies to all nuclei with cellular DNA synthesis only in the marginal chromatin. Moreover viral DNA synthesis is supposed in the cytoplasm, too. In methylnitroso urea-induced squamous cell carcinoma labeled cells were likewise found adjacent to keratinizing tumor regions and the pattern of DNA synthesis is generally not limited to the "stratum basale". With increasing malignancy the pattern of DNA synthesis is changing also in chemically induced tumors and is no longer limited to the stratum basale where it still can be demonstrated in the papilloma.

[Elimination of a paramyxo-type virus from oncornavirus-producing human cell lines (author's transl)]. / Eliminierung eines Paramyxovirus aus Oncornavirus-produzierenden menschlichen Zellinien

A virus of the paramyxo-type was eliminated from cell-free material of human oncornavirus-producing cell lines (PMF). After transmission of this paramyxovirus-free inoculum to a human permanent cell strain (Tu 197/Tr 1) oncornaviruses were permanently formed and no paramyxoviruses could be detected. The paramyxovirus-free, oncornavirus-producing PMF-39 cell line could be established after inoculation of the TU 197/Tr 1 line with cell-free material containing both oncorna- and paramyxovirus diluted 1 to 1000. A second way of elimination of the paramyxovirus was the treatment of cell-free material containing both viruses with antisera against paramyxovirus. In the Tu 197/Tr 1 line inoculated with such material only oncornaviruses were formed. The second paramyxovirus-free oncornavirus-producing cell line was designated PMF 50.

[C-type-like particles in normal human placentas (author's transl)]. / C-Typ-ähnliche Partikel in normalen menschlichen Plazenten

Evidence is presented for the presence of C-type-like particles in the syncytiotrophoblast of normal human placentas. In 10 of 110 mainly immature placentas studied both extracellular and budding particles were found.