The lack of v-src involvement in tumorigenicity of marmoset cells transformed in vitro with Rous sarcoma virus.

The transformation of nonhuman primate marmoset cells by Rous sarcoma virus of Schmidt-Ruppin strain (RSV-SR) generates transformants which lack tumorigenicity in allo- and xenogeneic hosts. Marmoset cells acquire this property when they are transformed by RSV rescued from non-tumorigenic allogeneic cells. One of the rescued RSV, when used to infect marmoset kidney cells in vitro, yielded transformants which became tumorigenic in adult allogeneic hosts.

Phorbol ester promotes growth and transformation of carcinogen-exposed nonhuman primate cells in vitro.

Kidney cells established in vitro from a white-lipped marmoset (106) were exposed to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) alone or in combination with 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Low (0.1 micrograms/ml, 4 times), intermediate (1 microgram/ml) and high (1 microgram/ml, 4 times) doses of MNNG resulted in 100%, 50% and 2.

Transformation of primate cells by chemicals and oncogenes: requirements for multiple factors.

Although several chemical carcinogenes have been shown to induce malignant transformation in human cells in culture, the molecular events involved in conversion of normal cells to malignant cells remain unknown at present. Normal human cells seem to be resistant to transformation by a single oncogene unless these cells have been immortalized by chemical carcinogens or DNA tumor virus genes. In some human cell systems, malignant phenotype is expressed after activation of protooncogenes probably through the mechanism of point mutations.

Chromosomal and c-K-ras oncogene alterations induced by a chemical carcinogen and phorbol ester in skin fibroblasts of individuals with familial polyposis coli.

Skin fibroblasts derived from three patients with familial polyposis coli (FPC) were treated in vitro with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) alone or in combination with the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA). None of the cultures treated four times with MNNG alone (1 microgram/ml) or in combination with TPA (eight applications, 0.1 microgram/ml each) showed either morphological transformation or anchorage-independent growth for 18 months after treatments.

The interaction of retrovirus and chemical carcinogen in experimental colon carcinogenesis.

The isolation and characterization of oncogenes from human colon cancer and the recognition of their homology with the ras gene of the Harvey and Kirsten strain of murine sarcoma virus (MSV) led us to investigate the effect of exogenous MSV on 1,2 dimethylhydrazine (DMH)-induced colon carcinoma in rats. DMH, 20 mg base/kg, was injected weekly for 10 weeks into Sprague-Dawley rats. The Moloney murine sarcoma virus (MSV-M) was injected (200 focus-forming units) intraperitoneally into 15 rats 48 hours after the last DMH injection or in 12 rats before the first DMH injection.

Adenovirus fiber protein produces synthesis of interferon in mouse spleen and macrophage cultures.

An inhibitor of viral activity appears in BALB/c mice spleen cells and macrophage cultures treated with adenovirus 2 fiber protein. This inhibitor was partially characterized and identified as type I interferon. Macrophage cultures produced higher titers of this interferon than did spleen cells.

Potential identification of chemical carcinogens in a viral transformation system.

Chemical carcinogens from several diverse chemical classes i.e.; aromatic amines, polycyclic hydrocarbons, nitrosamines, hormonal derivatives, metals and direct alkylating agents cause a 6.

Further studies on anti-tumor activity of adenovirus fibre protein on murine sarcoma tumours.

The present study demonstrates that subcutaneous injection of purified adenovirus 12 fibre protein (FP) to 4-week-old Balb/c mice, 4, 2 and 1 day(s) before intramuscular injection of murine sarcoma virus (MSV-M) or 2 and 1 day before and 1 day after MSV-M injection causes significant inhibition of tumour growth (P less than 0.001). The evidence suggests that treatment with FP leading to tumour inhibition is due to neither an interferon mechanism nor to inhibition of virus multiplication of FP in the reticuloendothelial system.

Inhibition of murine sarcoma virus induced transformation in an adenovirus -- NRK system.

Cell transformation induced by murine sarcoma virus (MSV-M) is significantly inhibited (80--90%) in a clonal line of normal rat kidney (NRK) cells when they are infected with rat cell passaged adenovirus 12 (R-Ad12). No inhibition is seen when R-Ad12 is added simultaneously with, or 1 1/2 or 24 hr after, MSV-M infection, suggesting that inhibition occurs most probably intracellularly. There is also a direct correlation between the extent of focus formation and the concentration of R-Ad12 used.

A variant of adenovirus 12 producing cytoplasmic accumulation of capsid proteins.

A variant of adenovirus type 12 (R-Ad12) has been isolated by infecting a clonal line of normal rat kidney cells (NRK) with wild-type adenovirus 12. Although R-Ad12 failed to produce infectious progeny virions when cycled a second time through NRK cells, it nevertheless retained the ability to code for virus structural proteins that accumulated in the cytoplasm.

Inhibition of murine sarcoma virus induced transformation by adenovirus structural proteins.

The purified fibre and hexon of adenovirus 12 inhibit the transformation in tissue culture of murine sarcoma virus (msv-m) by as much as 80% and 70%, respectively, when they are added to cells 8 to 2o h before MSV-M infection. During a 12 h period, only about 6 to 8% of added radiolabelled viral proteins become associated with cells (or I-O mug protein bound/10(5) cells). No inhibition occurs when the proteins are added simultaneously with MSV-M or 90 min or 4 h after MSV-M.

Antitumour activity of adenovirus-12 structural proteins against Moloney sarcoma tumours in mice.

When purified fibre and hexon proteins of adenovirus 12 were given intramuscularly to 4-week-old BALB/c mice (250-300 mug/mouse) 2 h prior to inoculation with mouse sarcoma virus (0.05 ml of 10(4) FFU/ml) at the same site, significant suppression of tumour growth (P less than 0.001), and rapid regression in tumour size (P less than 0.

Inhibition of melanoma growth in hamsters by type-2 adenovirus.

Type-2 adenovirus was shown to inhibit the growth of transplantable hamster melanoma in 70% of Syrian hamsters without any injurious effect to the host. Greatest inhibition of tumor formation was seen when animals were injected with 10(6) TCD50 of adenovirus and 2.5 x 10(5) tumor cells, or 10(6) TCD50 of virus and 5.

Adenovirus susceptibility to human interferon during one-step replication.

Susceptibility of adenovirus types 2, 7, and 12 to human interferon was measured in three human diploid cell strains during a single-cycle infection. Although the relative susceptibility of adenovirus to interferon varied in these cell strains, the final yield of each type in each cell strain decreased as the interferon dose increased. On the other hand, wide difference in interferon susceptibility of adenoviruses and vesicular stomatitis virus (VSV) was noted, as interferon doses above 100 units profoundly inhibited VSV but not the adenoviruses.

INTERFERENCE INDUCED AGAINST VACCINIA IN AN ADENOVIRUS-RHF-1 SYSTEM.

Khoobyarian, Newton (University of Illinois, Chicago). Interference induced against vaccinia in an adenovirus-RHF-1 system. J.

Rabbit heart cell culture, strain RHF-1. II. Behavior of adenovirus types 1 to 4.

Ankudas, Milda M. (University of Illinois, Chicago) and Newton Khoobyarian. Rabbit heart cell cultures, strain RHF-1.