Schmidt-Ruppin Strain Of Rous Sarcoma Virus Research Articles

The horizontal development of cell-mediated tumor-specific immunity in Rous sarcoma virus tumorigenesis in rats.

AbstractThe horizontal development of lymphoid cell‐mediated specific antitumor immunity was studied in R/F rats, inoculated with the Schmidt‐Ruppin strain of Rous sarcoma virus (SR‐RSV) during the neonatal period. Lymph‐node cells (LNC) were harvested from individual animals on consecutive occasions and used in colony inhibition tests for the detection of LNC‐mediated immunity to the Rous‐specific tumor‐associated transplantation antigen (s). None of the rats tested, which had been SR‐RSV inoculated within 6 days after birth, had any demonstrable LNC‐mediated immunity when tested within 4 weeks after virus inoculation. At the same time 68% of the rats SR‐RSV‐inoculated at a higher age disclosed a clear‐cut immunity. In the former group sarcomas appeared after short latency periods (average 5 weeks), while the latter group developed sarcomas with long latency periods (average 11 weeks) or remained tumor‐free. Also in tests performed later after SR‐RSV‐inoculation rats remaining tumor‐free or developing very late tumors tended to develop an LNC‐mediated immunity more rapidly than rats with tumors appearing earlier. The majority of both tumor‐positive and tumor‐negative animals developed at some time an LNC‐mediated immunity, which often persisted for several months in negative animals but sometimes disappeared in rats with a large tumor burden. The results indicate that the kinetics of the LNC‐mediated antitumor immune response can be of importance for the development of primary Rous sarcomas.

Influence of neonatal thymectomy upon the cell-mediated tumor-specific immunity in Rous sarcoma virus tumorigenesis in rats

The effects of neonatal thymectomy upon the output of thoracic duct lymphocytes (TDL), the yield of lymph node cells (LNC) and the cell-mediated immunity to the Rous-specific tumor-associated transplantation antigen(s) were studied in W Fu rats, inoculated with the Schmidt-Ruppin strain of Rous sarcoma virus (SR-RSV) at four weeks of age. Thymectomy diminished markedly the hourly TDL output, while the effect upon the total LNC yield was not significant. Cell-mediated immunity, registered by means of the colony inhibition technique, could be demonstrated both with TDL and with LNC with fairly good parallellity. In rats without palpable sarcomas and those carrying small tumors, respectively, cell-mediated immunity could be demonstrated in about the same frequency (around 50%) in thymectomized as in sham-operated rats, while in rats with large tumors a lower fraction of thymectomized animals disclosed such an immunity in comparison to sham-operated ones. The results indicate that neonatal thymectomy does not prevent the development of cell-mediated immunity to the Rous-specific tumor-associated transplantation antigen(s).

Transformation of human cells by virus and chemical carcinogen in vitro.

In vitro transformation of human embryo and uterine myoma cells was attempted by the Schmidt-Ruppin strain of Rous sarcoma virus (SR-RSV). In addition to single SR-RSV treatment, the combined effect of SR-RSV and 3-methylcholanthrene (MC) to human embryo cells was examined. Morphological transformation was observed within 3–4 weeks after SR-RSV infection. On the other hand, infectious virus was not detected in culture fluid, but viral genome was detected in all the SR-RSV infected cultures despite single or double treatment. The non-treated cultures and cultures treated with SR-RSV alone failed to produce a tumor in cortisone-conditioned hamster cheek pouch under the conditions of our experiments, but cultures treated with both MC and SR-RSV produced histologically malignant tumors. However, the growth rate of transformed human cells was not different from that of non-treated controls, and a stable line of transformed human cells could not be established in vitro.

Cell-mediated and humoral immune responses to tumor-associated and viral antigens in relation to the pathogenic effect of Rous sarcoma virus in rats.

AbstractAfter inoculation of the Schmidt‐Ruppin strain of Rous sarcoma virus (SR‐RSV) into a series of newborn rats (strain R/F) sarcomas developed in 47% of the animals, half of which also had hemorrhagic‐cystic lesions. In 18% such hemorrhagic cysts occurred without demonstrable tumors, while no pathogenic effect of the virus was observed in the rest of the animals.The colony inhibition technique was used to detect lymph‐node cell (LNC)‐mediated and humoral immunity to the tumor‐associated transplantation antigen (s). LNC‐mediated immunity could be demonstrated in a high proportion of tumor‐positive as well as tumor‐negative rats (83 and 94%, respectively), while the rats with hemorrhagic‐cystic lesions showed such immunity in a lower frequency (56%). Humoral cytotoxic activity could be demonstrated in a higher frequency in rats with cystic lesions than in rats without cysts, whether they had tumors or not (about 80 and 55%, respectively). Antiviral immune response was demonstrable in only a few animals.The results indicate that, as in several other systems, the development of tumors is not related to a deficient LNC‐mediated immune response to the tumor‐associated transplantation antigen (s). Nor could any difference be demonstrated in the frequency of humoral immune response to the antigen (s) between tumor‐positive and tumor‐negative animals. The results furthermore indicate that the hemorrhagic‐cystic lesions, characteristic for the RSV effect, develop in animals which have a less efficient LNC‐mediated immune response and that these lesions are of importance for the sustaining of humoral cytotoxic immune response.

The growth capacity of normal and Rous‐virus‐transformed chicken fibroblasts in vitro

AbstractThe proliferation dynamics of chicken embryo cells after transformation by Rous sarcoma virus, Schmidt‐Ruppin strain (RSV‐SR) has been investigated in vitro. The optimal schedule for serial cultivation for normal as well as transformed cells was to subcultivate the cells every third day using an inoculum of 50 X 104 cells per cm2 culture vessel area. Normal cells could be carried between 20–27 passages before they were lost in a degenerative phase similar to that described for normal human and other fibroblast‐like cells (Hayflick and Moorhead, 1961). The cumulative number of cells from a second passage inoculum of 2 × 106 cells varied between 109 and 1012. RSV‐SR transformed cells differed from normal cells in showing a decrease of the average population doubling time from 21 to 15 h and a two‐fold increase of their maximal terminal cell density. The life‐span of the RSV‐transformed populations was reduced to about 50% of the number of passages obtained by normal cells. The net result was a decrease of the cumulative cell number after transformation by RSV‐SR. No established RSV‐transformed or ‐untransformed lines could be developed.When RSV‐SR‐transformed cells of one sex were cocultivated with normal cells of the opposite sex a rapid transformation of the latter was observed. The proportion of dividing cells belonging to the originally transformed population gradually diminished until the cultures were completely dominated by freshly transformed cells.The results fit a previous hypothesis on the growth mechanism of avian Rous sarcoma (Pontén, 1964). RSV induces a change which enables the cell to proliferate at a faster than normal rate, to grow in an irregular manner in vitro, to reach higher than normal local densities in vitro and to invade surrounding normal tissues in vivo. None of these properties is permanent and the transformed or neoplastic cell populations will have a reduced total life span compared to their normal counterparts. Only if normal cells are constantly transformed and added to the proliferating pool of transformed or neoplastic cells will progressive growth prevail. The model is strictly applicable to stable systems (chicken, bovine, human); unstable species with a high spontaneous rate of transformation into established lines (mouse, rat, hamster) will react with the development of autonomously proliferating RSV cells capable of an infinite number of cell divisions.

Studies on group-specific antigens in tumours induced with avian tumour viruses in rats.

AbstractGroup‐specific complement‐fixing antigen (GS antigen) was studied by the complement‐fixation test in various avian and mammalian tumours, induced with the following strains of avian tumour virus (ATV): Schmidt‐Ruppin strain of Rous sarcoma virus (SR‐RSV), Prague strain of RSV (PR‐RSV), Fujinami sarcoma virus (FSV) and Bratislava 77 virus (B77V).All primary tumours induced in chicks by SR‐RSV, FSV and B77V, as well as all duck tumours induced with B77V, contained high titres of GS antigen when studied with high‐titre rabbit antiserum against purified GS antigen of avian myeloblastosis virus (AMV). In three out of six B77V‐induced rat tumours (two virus‐producing and one non‐virogenic) high titres of GS antigen were detected when examined with rabbit antiserum and with some rat sera obtained from tumour‐bearing animals. In three remaining B77V‐induced virogenic rat tumours (C21, C22 and C23), GS antigen was not detected with rabbit antiserum; however, sera obtained from these three tumour‐bearing rats contained high titres of GS antibodies when tested with different GS antigens. Positive results were obtained also with PR‐RSV‐induced virogenic rat tumour XC. However, all attempts to detect GS antigen in one SR‐RSV induced virogenic rat tumour (MRI) gave negative results. Possible heterogeneity of ATV‐induced GS antigen in mammalian tumours is discussed.

Interference phenomenon in the culture of chick embryo cells infected with Schmidt-Ruppin strain of Rous sarcoma virus.

Interference phenomenon which reduces the number of transformed foci in the culture of chick embryo cell (CEC) exposed to Schmidt-Ruppin strain of Rous sarcoma virus (SR-RSV) is described. The interfering substance(s) responsible for this phenomenon were detected and partially fractionated, and were also extracted from virus-infected chorioallantoic membranes (CAM). The amount of inhibitor(s) in the virus preparations was found to determine the number of cells registering as infective centers. Further, the inhibitor(s) we considered to consist mainly of inactivated virus particles and their degraded substances, suggesting that they are secreted from virus-infected cells into media during long culture.

Characterization of an Avian Leukosis Virus Isolate

An earlier publication reported the screening of hens from a commercial flock (Spring Lake Farms) for the purpose of selecting dams with which to establish a flock free of infection with agents possessing RIF (Resistance Inducing Factor) activity, i.e. the induction of cell resistance to Rous sarcoma virus (RSV) (6). An agent with RIF activity was isolated from cells representing the fourth passage in tissue culture of a pool of 4 embryos from 1 of the hens being screened. The results of further study of that isolate are presented here. Included are some physical and chemical characteristics, the antibody response it elicited in RIF-free chickens, and an antigenic comparison between this agent and the Bryan and Schmidt-Ruppin strains of RSV.

A heterogeneity of rous sarcoma virus revealed by selectively resistant chick embryo cells

A preparation of the Bryan high-titer strain of Rous sarcoma virus (RSV) was found to consist of two antigenically distinct variants, designated as RSV-1 and RSV-2. RSV-2 was immunologically related to, but not identical with avian myeloblastosis virus (AMV). RSV-1 showed no such relationship to AMV. RSV-2 differed further from RSV-1 by its growth properties in cell cultures derived from individual chick embryos. About 40% of the embryos from a commercial line of chickens gave tissue cultures resistant to RSV-2, whereas all embryos tested were sensitive to RSV-1. These differences between RSV-1 and RSV-2 proved to be controlled by two helper viruses, RAV-1 and RAV-2. RAV-1 shared with RSV-1 the antigenic makeup and the ability to grow in all chick embryos tested. RAV-2 was antigenically indistinguishable from RSV-2 and was unable to multiply in the same cells which were selectively resistant to RSV-2. The selective cellular resistance to RSV-2 was probably of genetic origin, since no evidence for the presence of an interfering avian leukosis virus could be found. The same resistance was also effective against the Schmidt-Ruppin strain of RSV and certain preparations of AMV.