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Biomedical subjects

R J Huebner

Publications and source records attributed to R J Huebner.

At least 37 records · Page 2Linked to original sources
PubMed1977

Characterization of human cells transformed in vitro by N-methyl-N'-nitro-N-nitrosoguanidine.

Human osteosarcoma (HOS) clonal cells transformed in vitro by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) were characterized, and compared to non-producer HOS cells transformed by Kirsten murine sarcoma virus (Ki-MSV). The MNNG- and virus-transformed cells grew in the aggregate form above an agar base, grew in soft agar, and had a high fibrinolytic activity. When inoculated into nude mice, all the chemically or virally altered cells produced tumors or tumor nodules. When transplanted into ATS-treated hamsters, the cells transformed by MNNG (0.01 mug/ml) and Ki-MSV produced tumors but MNNG (0.1 mug/ml) transformed cells did not produce tumors. The control HOS cells did not grow in the aggregate form but formed colonies in soft agar, and had low fibrinolytic activity and no capacity to form tumors in nude mice and ATS-treated hamsters. However, one of the control clonal lines had a high level of fibrinolytic activity. Cellular aggregation properties of human transformed cells did appear to correlate with tumorigenicity in nude mice.

Animals↗
PubMed1977

FeLV epidemiology in Los Angeles cats: Appraisal of detection methods.

We investigated the reliability of the fixed cell indirect fluorescent antibody (IFA) peripheral blood smear test as an index of systemic infection with FeLV. Positive results with this test were found to correlate well with detectable FeLV p30 antigen in bone-marrow smears by IFA, in serum and tissue by competition immunoassays, and with type-C particles in bone marrow or spleen by electron microscopy. Most cats with lymphoma, anemia or infectious peritonitis were positive for FeLV and showed a poor or absent antibody response to FeLV p30, gp70, and FOCMA antigens. Most older cats with lymphoma, carcinoma, or sarcoma were negative for FeLV expression and also lacked these FeLV-related antibodies. Detectable immunologic response to FeLV p30 and gp70 proteins and a high-titered FOCMA antibody response were generally restricted to certain healthy cats exposed to FeLV. Antibody to endogenous RD-114 viral p30 and gp70 was not detected in any of a large number of feline sera tested. The prevalence of FeLV-related diseases and immunologic responses to FeLV in healthy cats was directly correlated with the degree of FeLV exposure. By using the IFA blood smear and FOCMA antibody tests one can monitor the horizontal spread of FeLV in multi-cat household and accurately predict the FeLV disease susceptibilty or resistance of individual cats in each environments.

Adolescent↗
PubMed1977

Chemical transformation of rat cells infected with xenotropic type-C RNA virus and its suppression by virus-specific antiserum.

Fischer rat embryo cells infected with xenotropic mouse type-C RNA viruses isolated from either NIH Swiss mice or C57L inbred mice were transformed by 4-nitroquinoline oxide or 3-methylcholanthrene under conditions in which neither treatment alone sufficed to induce transformation. Transformation was dependent on the presence of actively growing virus at the time of chemical treatment. Specific antibody to xenotropic virus neutralized the virus and inhibited malignant transformation by 3-methylcholanthrene.

Animals↗
PubMed1977

Transformation of rat liver epithelial cells by Kirsten murine sarcoma virus.

We studied the transformation of epithelial, diploid cell lines (RL-33 and RL-34) derived from W rat liver by the Kirsten murine sarcoma virus. On days 4-5 after virus infection, the epithelial cells began to pile up focally, forming small projections and releasing round cells from the foci. The epithelial cells grew in chains or as islets and grew in suspension above the cells attached to the bottom of the flasks when the cultures reached the confluent stage. The virus titration pattern was "one-hit." Three classes of transformed cells were isolated with respect to virus release and antigen expression: 1) virus producer, 2) non-producer, and 3) sarcoma-positive, leukemia-negative cells. When transplanted sc into newborn rats, the transformed cells produced sarcomas. The transformed cells formed within 1-3 days larger aggregates than those of their normal counterpart cells when suspended in liquid growth medium above an agar base. Aggregate properties (size, viability, and proliferation) of transformed cells correlated with growth in soft agar and tumorigenicity. RNA-dependent DNA polymerase and type C virus particles were readily induced in the normal rat liver epithelial cells after exposure to 5-iodo-2'-deoxyuridine.

Animals↗
PubMed1976

Revertants of human cells transformed by murine sarcoma virus.

Revertants of nonproducer human osteosarcoma (NP/KHOS) cells induced by Kirsten murine sarcoma virus were isolated after incubating at high temperature (40.5 degrees C) overnight and subcloning at 36 degrees C. The morphologic variants, from which murine sarcoma virus could no longer be rescued, had growth properties similar to those of the nontransformed, parent human osteosarcoma cells and did not release RNA-dependent DNA polymerase activity. These revertants were nontumorigenic in nude mice. The revertants supported leukemia virus growth and showed an enhanced sensitivity to murine sarcoma virus superinfection. Thus, the revertants were from human cells transformed by an oncogenic RNA virus.

Cell Line↗
PubMed1976

The endogenous origin and transmission of RNA viral genomes that code for cancer.

In certain experimental animals, type-C virus genomes are universally prevalent. They are mostly but not exclusively transmitted genetically and produce tumors naturally as well as when transmitted experimentally. The spontaneous virus and tumor expressions are regulated and modified by genetic factors; and virus-specific virogenes used as vaccines prior to high-level natural expressions can suppress natural expressions of the virogenes. Application of this significant information to the prevention of cancer in mice now seems quite feasible; however its application to the control of human cancer is still dependent on the isolation of specific human type-C virus(es).

Animals↗
PubMed1976

The co-carcinogenic activity of 4-nitropyridine-1-oxide (4-NPO) and prevention of transformation by type-specific anti-viral antibodies.

Fischer rat embryo cells chronically infected with Rauscher murine leukemia virus, and known to be sensitive to transformation by potent chemical carcinogens, were transformed by the weak carcinogen 4-nitropyridine-1-oxide. Transformed cells grew in semi-solid agar and produced tumors in newborn Fischer rats. Transformation was inhibited by antisera specific for the ecotropic Rauscher murine leukemia virus, but not by antisera of equal toxicity specific for xenotropic Swiss mouse AT-124 virus.

4-Nitroquinoline-1-oxide↗
PubMed1976

Prevention of viral-chemical co-carcinogenesis in vitro by type-specific anti-viral antibody.

Low passage Fischer rat embryo cultures, which are normally very resistant to transformation by 3-methylcholanthrene but are highly susceptible when chronically infected with the Rauscher murine leukemia virus, were completely protected from transformation by methylcholanthrene when treated with neutralizing antibody specific for the leukemia virus prior to and during treatment with methylcholanthrene. Sister cultures were not protected by neutralizing antibody specific for the B-tropic radiation leukemia virus. This demonstrates clearly a definite type specific role for Rauscher murine leukemia virus in the 2-methylcholanthrene transformation system in rat cells.

Antibodies, Viral↗
PubMed1976

Prevention of spontaneous leukemia in AKR mice by type-specific immunosuppression of endogenous ecotropic virogenes.

AKR/J mice, 80-90% of which ordinarily die of spontaneous lymphocytic leukemias by 12 months of age, were significantly protected from developing leukemia in the initial experiment by a single course of treatment with AKR serotype-specific antibodies mad in goats and processed as immune gamma globulin (IgG). In experiment 1, IgG was given on the day of birth and on four additional days, and finished on day 14. This schedule resulted in suppression of over 4 logarithms of normal virogene expressions up to 25 days of age and led to partial viral suppression for over 200 days of age. At 365 days of age, 20 of 24 (83.3%) control animals were dead of leukemia whereas six of 30 (20%) treated animals had died of leukemia. In a second experiment, only four inoculations of IgG were given from birth to 20 days, after which they were given three inoculations of radiation-killed vaccine specific for AKR-Gross leukemia virus and one injection of murine sarcoma virus-Gross leukemia virus 10 days later. This combined immunization procedure provided significant virus suppression up to 288 days of age. At 300 days of age, 30 of the 50 (60%) controls had died of leukemia while only 1 of 24 (4.2%) of the immunized mice developed fatal leukemia; the significance of protection for each of the experiments was P LESS THAN 0.001. We conclude that these data establish in classical fashion with type-specific immunosuppression the determining role of type-C endogenous virogenes in leukemogenesis and, at the same time, also established the feasibility of nearly total prevention of leukemia in AKR mice.

AKR murine leukemia virus↗
PubMed1976

Suppression of murine type-C RNA virogenes by type-specific oncornavirus vaccines: prospects for prevention of cancer.

Immunization of crossbred and F1 mice with combined killed and live Gross leukemia virus AKR type-C viral vaccines suppressed endogeneous N-type AKR virus up to 10,000-fold for significant periods during early life. Since several previous studies in the same and similar crossbred systems revealed direct correlations between low and high levels of type-C virus early in life with low and high incidences of leukemia and other cancers later in life, we believe that prospects for suppression of spontaneous neoplasms are good; however, 8-14 months will be required to achieve the final results. Should cancers be prevented by serotype-specific vaccines, such evidence would provide conclusive proof of endogenous viral etiology.

AKR murine leukemia virus↗
PubMed1976

Development of a lymphocyte transformation microassay for murine leukemia virus.

A lymphocyte transformation microassay (LTA) was developed from spleen harvests of 6- to 8-week-old BABL/cCr mice. The optimal culture conditions for the microassay were established by measurement of lymphoblastogenesis in response to phytohemagglutin (PHA) and pokeweek mitogen. Immunization, as measured by the LTA, of adult BALB/cCr mice with formalin-inactivated, sucrose-banded, murine type-C viruses was achieved with a three-dose regimen of 200, 100, and 100 mug during 3 successive weeks (Freund's complete adjuvant was used with the first dose). The ip route of immunization induced the best responses in lymphocytes harvested 18 days after the last immunogen was given. The LTA was consistently reproducible, limited only by biological variability of the mouse and the standardization of the antigen preparation. In mice immunized with Rauscher murine leukemia virus (R-MuLV) or AKR MuLV vaccine, the LTA was specific for the C-type virus and could be used to distinguish viral subtypes, because R-MuLV elicited responses significantly different from a B-tropic BALB/c leukemia virus. This specificity was evident when the stimulating antigen was presented as UV-inactivated, sucrose-banded virus or as freeze-thaw extracts of cell infected with MuLV.

Animals↗
PubMed1976

Effect of allelic substitutions at the hairless locus on endogenous ecotropic murine leukemia virus titers and leukemogenesis.

Leukemia-prone hairless (HRS/J; hr/hr) mice had significantly higher leukemia virus titers than did the leukemia-resistant nonmutants (hr/ + and +/+). This difference was ascribed to the allelic substitution at a single gene locus; at 6 months of age it averaged 13-fold, immediately preceding the large divergence in leukemia incidence between the mutant and nonmutant mice.

Alleles↗
PubMed1976

Type C virus expression in lymphoma-paralysis-prone wild mice.

Wild mice trapped near Lake Casitas (LC) in southern California showed a high prevalence of infectious type C virus in the liver, spleen, and thymus within the first few weeks of life. By young adulthood about 80% of LC mice (including their genital tissues) were infected. Virus isolates from these mice cause lymphoma and lower limb paralysis under both natural and experimental conditions. Mice destined to develop paralysis showed higher levels of serum gs antigen early in life, whereas mice destined to develop lymphoma or remain free of these diseases could not be distinguished by this test. The individual variation in virus expression suggested that differences in virus type or in the immune or other host defense mechanisms greatly influenced susceptibility or resistance to indigenous type C virus-caused disease in LC wild mice.

Age Factors↗
PubMed1976

Induction of lymphoma and associated xenotropic type C virus in C57L mice by whole-body irradiation.

Adult C57L mice received sublethal whole-body X-irradiation. Between 3 and 11 months later, 5 of the 7 exposed mice developed histopathologically confirmed malignant lymphomas (lymphocytic type) that primarily involved the thymus. The lymphomas were readily transplantable to other C57L mice of any age, which developed fetal lymphomatous involvement; the tumor cells could also be propagated in tissue culture. A xenotropic murine type C virus (MuX) was isolated from the cultured lymphoma cells after cocultivation with a permissive dog line. MuX activity was demonstrated by electron microscopy, complement fixation, indirect fluorescent antibody, infectivity, and genome rescue.

Animals↗
PubMed1976

Acceleration of transformation of rat embryo cells by rat type C virus.

Sprague-Dawley and Fischer rat embryo cells became spontaneously transformed about 20 passages after release of endogenous ecotropic type C virus (SD-RaLV and F-RaLV). The virus-producing transformed cells showed loss of contact inhibition, increased growth rate, and tumorigenicity in vivo. Exogenous infection of other Fischer rat embryo cultures in early passage with SD-RaLV and F-RaLV markedly accelerated their rates of transformation.

Animals↗
PubMed1976

The epidemiology and virology of C-type virus-associated hematological cancers and related diseases in wild mice.

In several different populations of wild mice, observed over a 35-month period in laboratory geriatric colonies, a direct correlation was found between the prevalence and titer of spleen complement-fixing gs (p30) antigen and C-type particles in newly trapped healthy mice and a predilection to lymphoma and a hind leg paralytic disease upon aging. Other studies have established the indigenous C-type virus as the essential etiological determinant of both diseases in wild mice. An increased incidence of breast carcinomas, hepatomas, and pulmonary adenomas associated with C-type virus also occurred in the lymphoma-paralysis-prone colony as compared with the tumor-resistant colonies.

Animals↗