Stimulatory effect of immunization on tumor induction by Moloney murine sarcoma virus.

Adult mice were immunized with varying doses of inactivated Moloney murine leukemia virus (M-MuLV). Eight weeks after immunization, mice were challenged with a dose of Moloney murine sarcoma virus (M-MuSV) that could induce tumors in approximately 50% of normal animals. Mice immunized with high doses of M-MuLV (10(10) particles) had significantly decreased tumor incidences, whereas mice immunized with low doses of M-MuLV (10(2) particles) had significnatly increased tumor incidences compared to those in nonimmunized controls. The stimulatory effect could be abrogated by the irradiation of mice with 450 rads 24 hours prior to M-MuSV challenge, whereas the inhibitory effect was resistant to this irradiation procedure. The results suggested that immunization with virus can either stimulate or inhibit virus-induced tumorigenesis, depending on the dose of virus used for immunization.     

In utero tumor induction by murine sarcoma virus (Moloney) in the rat. I. Biological characteristics

Female R rats mated with an R male and inoculated in utero, after fetectomy, with murine sarcoma virus (Moloney), developed tumors. These tumors originated in the uterus and were of fetal origin. Intravenous or intraperitoneal injection of the virus induced similar tumors. Infectious virus could not be isolated from the tumor cells kept as transplantable lines or cultured in vitro. However, the presence of the MSV genome could be demonstrated by a direct rescue test. In non-pregnant rats treated in the same way no neoplasms were recorded. The results are discussed in the light of current theories on the special immunological fetal-maternal relationship.     

In utero tumor induction by murine sarcoma virus (Moloney) in the rat. II. Histological and ultrastructural characteristics

On histological examination the twelve MSV-induced tumors in the uterus observed in our study proved to be of fetal origin. Ten of the 12 tumors had the histological and ultrastructural characteristics of a yolk-sac tumor. The two other tumors examined had a different morphological structure. One was classified as a teratoma with embryonal carcinoma, the other as a carcinosarcoma. In the primary neoplasms virus particles were found. Their ultrastructure was similar to that of MSV. The histology and the electron microscopy results are discussed in relation to the morphogenesis and the occurrence of these tumors in rodents as well as in man.     

Transformation of a mouse cell line by murine sarcoma virus (Moloney)

Murine sarcoma virus (Moloney) (MSV) transformed C3H2K cells originating from the kidney tissues of a newborn C3H/He mouse. Titration of the virus showed a one-hit dose response in the presence of an excess of Friend leukemia virus (FLV) and a two-hit dose response in the absence of FLV, indicating that MSV was defective and a dual infection by MSV and a murine leukemia virus was required for MSV focus formation. Preinfection with FLV interfered with focus formation by MSV. The MSV foci appeared most abundantly when the cells in the S phase were infected with the virus. Remarkable similarities between murine and avian sarcoma viruses were thus established. Focus center assay on either uninfected or FLV-infected C3H2K cell monolayer indicated that MSV foci did not arise by cellular division alone but required secondary infection, while RSV foci arose by cellular division alone.     

Effect of recombinant human interleukin 2 on the growth of a BALB/c sarcoma induced by Moloney murine sarcoma virus

The effect of in vivo administration of recombinant interleukin 2 (rIL2) on the growth of a primary female BALB/c sarcoma induced by Moloney murine sarcoma virus (M-MSV) was studied. Although low-dose administration of (6,000 JU/mouse x 14 days) rIL2 had no effect on the growth of the tumors, high-dose (15,000-80,000 JU/mouse x 14 days) intraperitoneal inoculation of rIL2 induced tumor regression, dose-dependently. Tumors in mice which received 80,000 JU/mouse/day of rIL2 regressed completely 2 weeks after the initiation of treatment. The survival rates of the treated groups were significantly higher than those of the control group. A time course experiment disclosed that the effect of rIL2 was restricted only to the group in which rIL2 treatment started 8 days after the inoculation of M-MSV. The cytotoxic activity of regional lymph node lymphocytes from rIL2-treated mice was demonstrated against primary culture of M-MSV-induced sarcoma but not against syngeneic tumor induced by methylcholanthrene (Meth A). The effect of rIL2 was partially blocked by the administration of anti-IL2 receptor antibody. Immunohistochemical examination revealed that infiltration of Thy1.2+Lyt1+2- (helper/inducer subset) lymphocytes into the tumor tissue was prominent in mice which received high-dose rIL2. The results indicated that IL2 induced regression of M-MSV-induced sarcoma mainly through activation of IL2-receptor-positive helper T cells in the tumor tissues and of killer cells in the draining lymph nodes.     

Resistance to Moloney murine sarcoma virus (M-MuSV) tumor induction is associated with natural antibody production to "endogenous" Moloney leukemia virus (M-MuLV) in BALB/Mo mice

BALB/Mo mice are characterized by early expression of "endogenized" M-MuLV and are resistant to M-MuSV tumor induction. Furthermore, compared to normal BALB/c mice, sera from BALB/Mo mice exhibit a significant reactivity which is specific for M-MuLV when tested in a 125I-labelled Staphylococcus protein A binding assay. The possible significance of this reactivity in conferring tumor resistance is explored.