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Biomedical subjects

R J Huebner

Publications and source records attributed to R J Huebner.

At least 19 recordsLinked to original sources
PubMed1983

Neoplastic transformation induced by adeno 12-SV40 hybrid virus in skin fibroblasts from humans genetically predisposed to cancer.

The DNA hybrid adeno 12-SV40 virus induced neoplastic transformation of human skin fibroblasts derived from individuals with adenomatosis of the colon and rectum (ACR), an inherited cancer syndrome. The line established from the transformed ACR fibroblasts became stable and was initially virus productive, but infectious hybrid virus gradually decreased over serial passages. Cultured skin fibroblasts from normal individuals infected with adeno 12-SV40 also underwent morphological transformation and were virus productive. Although these cells had a prolonged life as compared with uninfected controls, they eventually died. All of the transformed cells contained both adeno 12 and SV40 large tumor antigens, formed large cell aggregates, grew in liquid growth medium above an agar base, and formed colonies in soft agar. The altered ACR cells became heteroploid and produced tumors when transplanted subcutaneously into nude mice. The results suggest that ACR individuals have increased susceptibility to neoplastic transformation by oncogenic tumor viruses.

Adenoviruses, Human↗
PubMed1981

Unusual filterable oncogenic agent isolated from horizontally transmitted Syrian hamster lymphomas.

An outbreak of horizontally transmitted malignant lymphoma in an experimental hamster holding facility was previously reported. Retroviridae (oncornavirus) or other conventional oncogenic viruses (oncodnaviruses) could not be detected in these lymphomas by immunological methods, direct isolation procedures or electron microscopy but an infectious agents was clearly involved. The incidence of lymphomas during five recurrent epidemics ranged from 50 to 90% in young, inbred and random-bred Syrian golden hamster exposed. The agent seemed to be resistant to UV inactivation, formaldehyde vapour and other viricidal agents (chlorine and iodine), and stable for long periods in the absence of hamster hosts in the contaminated facility. Associated disease syndromes in exposed hamster included severe enteritis, pyelonephritis, the occasional appearance of warts, poor breeding efficiency and intussusception. We now report the successful, cell-free isolation of an unusual, filterable agent prepared in protamine sulphate buffer from primary and animal-passaged lymphomas, which produces lymphomas with good efficiency when injected subcutaneously (s.c.) into newborn Syrian inbred (LSH) and random-bred (LVG) hamster. The agent could be reisolated from these induced lymphomas and injected into other hamsters to reproduce the neoplastic condition. It showed characteristics suggested for a mammalian viroid (a non-encapsidated, DNase-sensitive low-molecular-weight, disease-causing, self-replicating, naturally infectious nucleic acid).

Age Factors↗
PubMed1981

Neoplastic transformation of chimpanzee cells induced by adenovirus type 12--simian virus 40 hybrid virus.

The adenovirus 12--simian virus 40 hybrid virus produced neoplastic transformation of chimpanzee skin fibroblasts in vitro. The transformed fibroblasts showed morphological alteration and became permanent lines. The transformed cells contained both adenovirus 12 and simian virus 40 large tumor antigens and were virus producers. However at passage 9, one line (WES) was found to be a nonproducer, producing neither infectious virus nor virus-specific antigen detectable by the complement fixation test. Virus particles were not detected nor could infectious hybrid virus be rescued from this line by cocultivation with Vero cells. The transformed cells formed large cell aggregates and grew in liquid growth medium above an agar base, formed colonies in soft agar, and grew to high saturation densities; the normal chimpanzee skin fibroblasts did not. One transformed WES line produced tumors when transplanted subcutaneously into newborn nude mice, thus providing an important tool for studying tumor immunity in the chimpanzee.

Adenoviruses, Human↗
PubMed1981

Prevention of 3-methylcholanthrene-induced fibrosarcomas in rats pre-inoculated with endogenous rat retrovirus.

Weanling Fischer 344 rats received a single intraperitoneal injection of a 1000-fold concentrated preparation of endogenous nontransforming rat retrovirus. Ten days later, the rats were each given a single subcutaneous injection of 3-methylcholanthrene. The rats inoculated with the endogenous rat retrovirus were significantly protected against the development of cancer, whereas uninoculated rats and rats given one of several murine retroviruses or baboon retrovirus were not protected.

Animals↗
PubMed1981

Prevention of tumors in rats by cross-protective immunization.

F344 inbred were repeatedly immunized (days 0, 28, and 42) with normal syngeneic or allogeneic rat tissues or transplantable syngeneic or allogeneic rat tumors (some of which were virus producing). Immunized rats were challenged by sc injection of 10(5) or 10(6) syngeneic rat tumor cells from either of two different tumor lines. Successful cross-protective immunization prevented tumor development in rats that were challenged at 100-1,000 times the 50% tumor dose. The protection was essentially lifelong and complete in that no tumors appeared up to 200 days post challenge in some experiments. To be successful, the tumor cell vaccines had to express a complement-fixing cross-reacting antigen detected with sera from rats bearing any of several different tumors and to be able to induce a spontaneously regressing tumor in the host.

Animals↗
PubMed1981

Chemical transformation of cultured skin fibroblasts from humans genetically predisposed to cancer.

Adenomatosis of the colon and rectum (ACR) is an inherited form of cancer. Assuming that phenotypic expressions that appear in cell strains reflect its biological abnormalities, the study of cultured skin fibroblasts derived from individuals with an inherited form of cancer such as ACR provides a unique study for analysis of the oncogenic process. Growth disorders and increased susceptibility to tumor promoters and to transformation by an oncogenic RNA tumor virus have been demonstrated in these skin fibroblasts. We found that human skin fibroblasts (PF) derived from ACR individuals were sensitive to a chemical carcinogen. Cells treated only with various levels of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) underwent morphological alteration. The morphologically altered cells formed large cell aggregates when suspended in liquid growth medium above an agar base and grew to high saturation densities but did not form colonies in soft agar. Transformed cells were resistant to rechallenge of MNNG (1 microgram/ml) and showed prolonged life span compared to those untreated cells. However, no tumors were produced when cells were inoculated subcutaneously into nude mice. Data suggest that neoplastic transformation of these skin cells by chemical carcinogens is a multi-phase process.

Cell Transformation, Neoplastic↗
PubMed1980

Chemical transformation of cultured human skin fibroblasts derived from individuals with hereditary adenomatosis of the colon and rectum.

Chemical transformation of cultured human skin fibroblasts (PF) derived from individuals with hereditary adenomatosis of the colon and rectum is reported. Cells treated only with various levels of N-methyl-N'-nitro N-nitrosoguanidine (MNNG) underwent morphological alteration. The morphologically altered cells formed large aggregates when suspended in liquid growth medium above an agar base and grew to high saturation densities. One altered (MNNG, 1.0 microgram/ml) cell culture formed colonies in soft agar. Transformed cells were resistant to rechallenge of MNNG (l microgram/ml) and showed a more prolonged life-span compared to the untreated cells. Altered cells became heteroploid cells. However, no progressively growing tumors were produced when cells were inoculated subcutaneously into nude mice. The data suggest that chemical carcinogens alone may not induce neoplastic transformation of fibroblasts from humans genetically predisposed to cancer and that neoplastic transformation of these skin cells by chemical carcinogens might require the presence of a tumor promotor and the use of an immuno-privileged site in the nude mouse system.

Adenoma↗
PubMed1979

Prevention of spontaneous leukemia in mice by oncornavirus immunization.

C57L, NIH, and SWR mice were immunized with inactivated Gross leukemia virus (GLV) and then mated with AKR males. Their F1 offspring were then immunized with the murine sarcoma virus pseudotype of GLV, MSV(GLV). The concentrations of infectious ecotropic AKR virus in tail extracts of immunized mice were 100- to 1,000-fold lower than in non-immunized controls when tested at 30--40 days of age. Although viral titers increased slightly with time, the titers remained at least one log10 lower in the immunized mice than in non-immunized F1 control mice at all times tested. The reduction in the level of expression of endogenous ecotropic virus showed a highly significant positive correlation with the reduction in incidence of spontaneous leukemia in these mice. These data thus show that successful immunoprevention of leukemia in mice can be achieved with viral vaccines.

AKR murine leukemia virus↗
PubMed1979

Induction of rat sarcomas in rats treated with antithymocyte sera after transplantation of human cancer cells.

Human cancer cells that had had high (greater than 160) tissue culture passages, when transplanted into antithymocyte-treated F344 newborn rats, caused induction of rat sarcomas in the rats within 2 or 3 subcultures, whereas human cancer cells with low (5-33) passages in vitro did not cause overt induction of rat sarcomas until after 5-10 subtransplantations. Because oncornavirus activity was not detected in either rat or human tumors, it is suggested that transforming sequences located on the human tumor cells may have been transferred to supporting rat reticulum cells in close contact with the human cancer cells.

Animals↗
PubMed1979

Prevention of spontaneous leukemia in AKR mice by passive immunization and type specificity of this protection.

AKR mice were given sc injections of goat antiviral immune globulin from birth through 14 or 31 days of age. Although the shorter immunization schedule greatly reduced expression of spontaneous leukemia, the longer immunization period was required for essentially complete prevention of leukemia. Immune globulin with a high neutralization titer for ecotropic virus provided this protection, whereas antibody with a high neutralization titer for murine xenotropic virus did not.

Animals↗
PubMed1979

Prevention of transplantable tumors by adoptive transfer of spleen cells from immunized rats.

Fischer 344 rats were specifically hyperimmunized with allogeneic, nonvirus-producing [Kirsten murine sarcoma virus (KiMSV)] or syngeneic, virus-producing [KiMSV (Rasheed)] rat tumors. Spleen cells taken from these rats adoptively transferred protection against a 100 to 1,000 X rat tumor dose50 cell challenge with several different transplantable rat tumors. Protection was obtained with spleen cells after removal of adherent cells and macrophages but not peritoneal cells. The spleen cells were not directly cytotoxic but required more than 3 days residence in the recipient before protecting the recipient against challenge. No protection against tumor cell challenge was observed when spleen cells were lethally x-ray irradiated before injection into nontreated rats. Spleen cells taken from rats immunized with normal histocompatibility antigens did not protect in this test system.

Animals↗
PubMed1978

In vitro and in vivo indications of the carcinogenicity and toxicity of food dyes.

Eight food dyes or commercial color mixtures certified for use in the United States were tested for their ability to transform in vitro a serial line of Fischer rat embryo cells previously reported to be a sensitive indicator of chemicals having carcinogenic potential. Malignant cell transformation was induced by a commercial mixture (G2024) of two of these dyes (Blue 1 and Yellow 5) and by Blue 2, Green 3 (one of two experiments) and Red 4. Food dyes Blue 1, Red 3, Yellow 5 and Yellow 6 did not induce cell transformation. One to 1.5 mg of each dye was injected into suckling LVG or Graffi hamsters which were monitored for tumor induction and/or death over a 330-day period. None of the non-transforming dyes (Blue 1, Red 3, Yellow 5, Yellow 6) or Green 3 induced a significant increase in tumor (mostly lymphoma) incidence or animal mortality. Three of the transforming dyes (Blue 2, Green 2024, Red 4) did increase tumor incidence and/or mortality in at least one strain of hamster. We conclude the the in vitro assay suggested that certain food dyes were carcinogens and that in vivo studies in hamsters supported this interpretation.

Animals↗
PubMed1978

In vitro isolation of stable rat sarcoma viruses.

A Sprague-Dawley (SD-1) rat embryo culture, at low passage level, released an endogenous ecotropic type C virus (SD-RaLV) and after about 20 further passages it underwent spontaneous transformation. The SD-RaLV, released from the transformed cells, did not cause rapid transformation of other rat embryo cells. However, when the transformed cells were repeatedly cocultivated with three different chemically transformed and serially transplanted rat tumor cell lines (sarcoma, carcinoma, and hepatoma), rapidly fibroblast-transforming "sarcoma" viruses (RaSV) were recovered after each attempt. RaSV was not recovered from one of these tumor cell lines before transplantation, nor could focus-forming virus be rescued from these same tumor cells by cocultivation with other cells releasing heterologous type C viruses. Foci were induced on normal rat kidney and several other rat embryo cell strains within 7-15 days and both productive and nonproductive NRK clones were derived. The productive clones were positive for rat specific p30 antigen and the RaSVs released were serially transmitted to other rat embryo cells. RaSV genome was rescued from the nonproductive clones by superinfection with SD-RaLV, wild rat type C virus, and several heterologous type C viruses. These observations appear to represent naturally occurring transformation-specific (src) genes being recovered in vitro in the form of stable "sarcoma" viruses. These viruses differ from the Kirsten and Harvey strains of murine sarcoma virus in that they apparently contain no MuLV sequences and are of purely rat origin.

Animals↗