Search PubMed⌕ Search

Biomedical subjects

C W Boone

Publications and source records attributed to C W Boone.

At least 127 records · Page 7Linked to original sources

Common tumor rejection antigens in methylcholanthrene-induced squamous cell carcinomas of mice detected by tumor protection and a radioisotopic footpad assay.

Seven transplantable lines of squamous cell carcinoma of the skin initiated in BALB/c mice by skin painting with methycholanthrene were systematically tested for cross-reactivity of their tumor rejection antigens in a 7 X 7 matrix. As determined by decreased tumor frequency after tumor cell challenge, each line was immunogenic against and/or immunosensitive to at least one and usually more than one of the other lines. A radioisotopic footpad assay for delayed hypersensitivity against viable tumor cells confirmed the cross-reactivity shown by tumor rejection. More than two antigens appeared to be present in the lines. Tests for C-type viruses were positive in all tumors; those for polyoma virus were negative. Whether the uniform presence of C-type viruses can account for the number and variety of antigens found, or whether the tumor rejection antigens are independent of virus expression, remains an open question. The finding of cross-reacting tumor rejection antigens in methylcholanthrene-induced squamous cell carcinomas encourages prospects for the development of more broadly applicable immunodiagnostic and immunotherapeutic reagents.

Animals↗

Augmented immunogenicity of tumor cell membranes produced by surface budding viruses: parameters of optimal immunization.

Membranes prepared from tumor cells infected with surface budding viruses are much more immunogenic than membranes from uninfected tumor cells. Factors affecting immunization with membranes from virus-infected tumor cells were studied. Preparations made with influenza virus were clearly superior to those prepared with vesicular stomatitis virus (VSV). Membranes infected with VSV were maximally immunogenic at a dose equivalent to a 10% cell pack whereas influenza-virus-infected membranes were immunogenic at 1/100th of this dose. Subcutaneous inoculation was better than other routes of administration. Maximum protection against challenge with viable tumor cells was afforded by two inoculations of VSV-infected membranes spaced 3 days apart or a single inoculation with influenza-virus-infected membranes. Administration of membranes in complete Freund's adjuvant either had no effect of induced a slight degree of tumor enhancement. Immunization with influenza-virus-infected membranes significantly reduced tumor size and incidence even at a challenge dose of tumor cells which was 50 times the LD100.

Animals↗

Sarcomas routinely produced from putatively nontumorigenic Balb/3T3 and C3H/10T1/2 cells by subcutaneous inoculation attached to plastic platelets.

The Balb/3T3 and C3H/10T1/2 lines, noted for their marked postconfluence inhibition of proliferation and anchorage dependence, and frequently studied as non-tumorigenic lines that are compared with tumorigenic sublines transformed with various agents, produced tumors within two to four months at low-cell dosage (3 X 10(4) cells) when implanted subcutaneously attached to 1 X 5 X 10 mm polycarbonate platelets. Platelets alone did not produce tumors. The cultured Balb/3T3 tumor cells showed loss of both postconfluence inhibition of proliferation and anchorage dependence. Tumors arising from attached Balb/3T3 cells in (BALB/c X C57B1/6)F1 hybrids were shown to be transplantable to BALB/c but not to C57B1/6 mice, proving that the tumors were derived from Balb/3T3 and not from host cells. The tumors exhibited unique transplantation rejection antigens that did not cross-react with each other. Scanning electronmicroscopy of Balb/3T3 cells and derived tumor cells on Teflon substrates (on which only the tumor cells and not the parent Balb/3T3 cells could grow) revealed that the two cell types were remarkably similar in appearance, except that the tumor cells were larger and showed many more microvilli that tended to concentrate over the nucleus. We conclude that Balb/3T3 cells and C3H/10T1/2 cells are preneoplastic and give rise to spontaneously transformed clones when implanted in vivo attached to a solid substrate.

Animals↗

Comparison of foundry dust evaluation by various methods.

Matched sets of dust samples were collected in gray iron foundries for the purpose of comparing results obtained by four sampling techniques. Both respirable and total dust samples were collected. The results are compared on the basis of total concentration and on the basis of silica content. The problems in obtaining an adequate sample for silica analysis are considered. A proposal is made for using total respirable dust as an index of permissible dustiness in foundries.

Air Pollutants, Occupational↗

Local adoptive transfer of antitumor cellular immunity to xenogeneic animals studied with a rapid radioisotopic footpad assay.

The antitumor cellular immune response to Gross virus-induced rat tumor cells in F344 rats, as measured by a sensitive radioisotopic footpad assay, was adoptively transferred to syngeneic rats and to xenogeneic irradiated BALB/c mice. Xenogeneic transfer was accomplished by the injection of a mixture of rat tumor cells and syngeneic spleen cells, peritoneal exudate cells, or blood lymphocytes from specific immune rats into the footpads of mice. Peritoneal exudate cells produced the strongest footpad reaction in xenogeneic recipients. Use of the xenogeneic adoptive transfer system in a bioassay for human antitumor immunity appeared feasible.

Animals↗

Expression of virus structural proteins on murine cell surfaces in association with the production of murine leukaemia virus.

We have used a quantitative radiolabelled antibody procedure to measure the amount of certain virus structural antigens on the surface of BALB/c RAG cells producing endogenous B-tropic type C virus. RAG cells expressed group specificities of MuLV p30 on their cell surface but did not express gp70 group specificities. However, type specificities of gp70 were expressed on BALB/c cell lines infected with Moloney leukaemia virus. The majority of p30 antigens detected on the RAG cell surface were removed by trypsin and their reappearance was prevented by cycloheximide, even in the presence of 'conditioned medium' containing MuLV. Passive adsorption of exogenous MuLV p30 to the surface of virus negative BALB/c fibroblasts reached a maximum of 20% of the protein detectable on virus producing RAG cells. These data support the hypothesis that much, but not all, of the surface p30 is expressed de novo on the cell membrane and not derived from passive adsorption of p30 released from shed virus or as a by-product of virus infection of a cell.

Adsorption↗

Discussion paper: specific paralysis of the antitumor cellular immune response produced by growing tumors studied with a radioisotope footpad assay.

The kinetics of the antitumor cellular immune response of mice with progressively growing syngeneic tumors were determined in vivo using a quantitative radioisotopic footpad assay. A close correlation was found between the size of the tumor and the degree of the cellular immune response. An initial phase of cellular immune stimulation was followed by specific suppression and subsequent immunologic paralysis as the tumor grew larger. This immune paralysis was attributed to increased tumor load since a homogenate of an SV40 transformed fibrosarcoma injected intraperitoneally into tumor-immune mice specifically depressed their cellular immune response. The fraction of the tumor homogenate that brought about this depression was present in the high speed supernatant and pellet of a 3M KCl extract of the tumor. The specificity of the depression was determined in vivo by the radioisotopic footpad assay and in vitro by a 51Cr cytolysis assay. Unwashed spleen cells harvested from mice bearing large tumors were unreactive in a local adoptive footpad assay. However, reactivity could be restored by repeatedly washing the spleen cells.

Animals↗

Adoptive immunotherapy of a Gross virus producing lymphoma and a methylcholanthrene-induced fibrosarcoma in tolerant rats.

Immunological tolerance to Gross virus-specific transplantation antigens in rats given neonatae transfer of donor lymphoid cells beneath the kidney capsule of syngeneic recipient rats. Immune or normal donor cells invariably developed a cell-mediated immune reaction in kidneys of GV-tolerant recipients, presumably against GV antigens present on the surface of recipient lymphoid cells in the kidney. Spleen and lymph node cells from tolerant rats failed to develop a reaction in tolerant recipients, but developed a strong reaction to histoincompatible antigens in the kidneys of semisyngeneic tolerant rats. The immunologically tolerant state in the rats could be broken by adoptive transfer of spleen and lymph node cells from syngeneic rats immunized with GV-induced lymphoma cells. Immunotherapy of a GV-induced and also a GV-infected methylcholanthrene-induced fibrosarcoma growing in tolerant rats was successful when immune spleen and lymph node cells were administered i.p. 3 days after s.c. inoculation of 2 X 10(7) tumor cells in the case of the lymphoma, and 1 day after inoculation of 5 X 10(6) tumor cells in the case of the fibrosarcoma.

AKR murine leukemia virus↗

Vasoformative sarcomas arising from BALB/3T3 cells attached to solid substrates.

The BALB/3T3 mouse embryo cell line, noted for its marked postconfluence inhibition of proliferation, anchorage dependence, and high serum requirement, and frequently studied as a prototype nontumorigenic "fibroblast" line that is compared with tumorigenic sublines transformed with various agents, produced tumors within 2 to 3 months when an average of 3 X 10(4) cells were implanted s.c. attached to 1- X 5- X 10-mm polycarbonate platelets. Plastic platelets alone produced no tumors after 1 year of observation. The tumors, as well as others arising from implants of BALB/3T3 cells attached to 3-mm glass beads, were given the histological diagnosis of "vasoformative saroma" because the tumor cells frequently formed vascular channels. The vasoformative pattern and the results of specific staining for reticulin and collagen support the likelihood that BALB/3T3 cells originated from endothelial cells rather than from fibroblasts. That the tumors were derived from BALB/3T3 cells and not host cells was proved when tumors arising in BALB/c X C57BL/6 F1 hybrids were shown to be transplantable to BALB/c but not to C57BL/6 mice. The cultured tumor cells showed loss of both postconfluence inhibition of proliferation and anchorage dependence. Evidence of the induction of endogenous oncornaviruses was obtained in only one of four tumors tested. These tumors also exhibited tumor-unique transplantation rejection antigens. We conclude that BALB/3T3 cells are preneoplastic and give rise to different spontaneously transformed clones bearing unique tumor rejection antigens when implanted in vivo attached to a solid substrate.

Animals↗

Karyotypes of vasoformative sarcomas arising from BALB/3T3 cells attached to polycarbonate plates.

Four vasoformative sarcoma in vivo tumor lines arising from the s.c. implantation of 3 X 10(4) BALB/3T3 cells attached to a 1- X 5- X 10-mm polycarbonate platelet were shown to be quite similar in chromosome constitution to the parental 3T3 line. All tumors contained the same marker chromosomes that were present in the parent BALB/3T3 cells. The findings conclusively showed that the tumors had derived from BALB/3T3 cells and not from host cells or from the in vivo fusion of the inoculated 3T3 cells with host cells. Each tumor line had a unique karyotype that was markedly more homogeneous than that of the parental BALB/3T3 cells, strongly suggesting that each tumor represented a separate clone. An M1 marker chromosome was consistently present in each of the four tumor lines but was present in only about 50% of the parent BALB/3T3 cells; it therefore appeared to be a distinct and stable feature of the tumors.

Animals↗

Accelerated regeneration of trypsin-treated surface antigens of simian virus 40-transformed BALB/3T3 cells induced by X-irradiation.

The antigens of SV40-transformed BALB/3T3 cells measured by a radioisotopic footpad assay after removal by trypsin treatment regenerated in vitro in 3 to 6 hr. After X-irradiation with 3000 R, however, the antigens were regenerated to normal levels within 1 h. X-ray doses of between 1000 and 5000 R accelerated the regeneration of cell surface antigens, while X-irradiation with the larger dose of 8000 R did not. X-irradiation of nontrypsinized tumor cells was without effect. Possible mechanisms of this phenomenon are discussed.

Animals↗

Local adoptive transfer to mice of human delayed hypersensitivity: reactions by the radioisotopic footpad assay.

Human delayed hypersensitivity to living BCG organisms and/or Varidase was adoptively transferred to mice and assayed in mice by a radioisotope footpad assay (FPA). A mixture of the antigen and peripheral blood lymphocytes from patients (positive skin reactions to PPD and/or Varidase) or healthy volunteers was inoculated into the footpads of lethally X-irradiated mice. A positive footpad reaction was accompanied by an increased leakage of the radiolabelled serum protein from the blood stream into the intercellular space at the site of inoculation, and was measured by the 'foot-count ratio', or radioactivity in the test foot divided by radioactivity in the contralateral foot. The intensity of the footpad reaction correlated directly with the skin test response of the human lymphocyte donors.

Adolescent↗

Malignant hemangioendotheliomas produced by subcutaneous inoculation of Balb/3T3 cells attached to glass beads.

The Balb/3T3 mouse embryo cell line has been frequently used in cancer research as representative of nontumorigenic cells with the characteristic in vitro properties of postconfluence inhibition of cell division, low saturation density, and anchorage dependence. On the reasoning that anchorage dependence might also apply in vivo, each of nine mice were subcutaneously inoculated with an average of 15,400 Balb/3T3 cells attached to two glass beads 3 millimeters in diameter. After 8 weeks, all the mice had developed large bloody tumors that microscopically proved to be hemangioendotheliomas. Ther inoculation of Balb/3T3 cells alone or beads alone produced no tumors. Transplants of each tumor into normal mice grew to kill the animal within 6 weeks. Tumor cells from collagenase-disaggregated tumor tissue had a plating efficiency of 21.2 percent compared to that of normal adult subcutaneous fibroblasts of less than 0.1 percent. The tumor cells in vitro closely resembled Balb/3T3 cells in appearance and were tumorigenic at a dose of 10-4 cells. A second, repeat experiment produced the same type of tumors grossly and microscopically in 17 of 25 mice between 99 and 211 days after inoculation of the Balb/3T3 cells attached to glass beads. These findings require a reassessment of the postulate that low saturation density, postconfluence of cell division, and anchorage dependence are characteristic in vitro properties only of nonneoplastic cells.

Animals↗

Local adoptive transfer of the antitumor cellular immune response in syngeneic and allogeneic mice studied with a rapid radioisotopic footpad assay.

The immunologic nature of the cellular immune response against tumor cells inoculated in the footpad of mice was studied with a rapid, quantitative, and specific assay. The results indicate: a) The antitumor cellular immune response could be transferred adoptively in syngeneic and allogeneic mice with specific immune thymus (T) lymphocytes isolated on nylon columns; b) T-independent cells of host origin were necessary for the manifestation of the antitumor footpad reaction; and c) there was a close correlation between immune responses detected by the footpad assay and those detected by transplantation techniques. The footpad reaction consisted of several nonspecific and specific components. Nonspecific factors disturbing the specific footpad reaction in syngeneic and allogeneic recipients were discussed.

Animals↗