Neoplastic conversion of human keratinocytes by adenovirus 12-SV40 virus and chemical carcinogens

Efforts to investigate the progression of events that lead human cells of epithelial origin to become neoplastic in response to carcinogenic agents have been aided by the development of tissue culture systems for propagation of epithelial cells. In the present study, nontumorigenic human epidermal keratinocytes immortalized by adenovirus 12 and simian virus 40 (Ad 12-SV40) were transformed by treatment with the chemical carcinogens N-methyl-N'-nitro-N-nitrosoguanidine or 4-nitroquinoline-1-oxide. Such transformants showed morphological alterations and induced carcinomas when transplanted into nude mice, whereas primary human epidermal keratinocytes treated with these chemical carcinogens failed to show any evidence of transformation. This in vitro system may be useful in assessing environmental carcinogens for human epithelial cells and in detecting new human oncogenes.     

Murine leukemia virus: high-frequency activation in vitro by 5-iododeoxyuridine and 5-bromodeoxyuridine

Cells of embryos of the high leukemic mouse strain AKR can be grown in culture as virus-negative cell lines. However, these lines and clonal sublines uniformly have the capacity to initiate synthesis of murine leukemia virus. Exposure of the cells to 5-iododeoxyuridine or 5-bromodeoxyuridine induced synthesis of virus in as high as 0.1 to 0.5 percent of the cells; many of the cells were producing virus as soon as 3 days after initiation of treatment. Induction of virus by these drugs is several orders of magnitude greater than that obtained with any other treatment tested. These studies indicate that the full genome of murine leukemia virus is present in an unexpressed form in all AKR cells and provide a potentially powerful technique for activating leukemia virus genomes in other cell systems.     

A transforming ras gene in tumorigenic guinea pig cell lines initiated by diverse chemical carcinogens

Fetal guinea pig cells were transformed by treatment with four different chemical carcinogens including nitroso compounds and polycyclic hydrocarbons. As a consequence of this treatment, oncogenes capable of transforming NIH/3T3 cells became activated in each of five independently established clonal guinea pig cell lines. Molecular characterization of representative NIH/3T3 transformants revealed that the same oncogene was present in each of the cell lines tested. Moreover, detection of this transforming gene paralleled the acquisition of tumorigenic properties by these neoplastic cells.     

Mouse leukemia: depression of serum interferon production

Production of circulating interferon is significantly impaired in AKR/J mice after development of lymphoblastic leukemia and in Balb/c mice with clinical signs of Friend erythroblastic leukemia. This alteration has been observed with three interferon inducers, each one known to elicit an interferon response in different cells.     

Limitations of metabolic activation systems used with in vitro tests for carcinogens

Important differences between the metabolic activation of 7,12-dimethylbenz[a]anthracene in intact cellular systems and in liver homogenates suggest that the use of homogenates in conjunction with short-term assays for carcinogens could yield misleading results.     

Suppression of gamma interferon production by inactivated feline leukemia virus

Supernatants from cultures of normal feline lymphocytes stimulated with Staphylococcus enterotoxin A showed antiviral activity, characterized as a gamma-like interferon. With the addition of inactivated feline leukemia virus, markedly less interferon was produced. The reduction in interferon production was not attributable to lowered lymphocyte viability or reduced mitogenic properties of Staphylococcus enterotoxin A and appears to be a direct retroviral effect. This finding may reflect clinically relevant events that may contribute to the development of the feline or human states of acquired immunodeficiency.     

Activation of spontaneous murine leukemia virus-related antigen by lymphocytic choriomeningitis virus

Persistent infection with lymphocytic choriomeningitis (LCM) virus activates a phenotypic expression of murine leukemia viruis-related antigen. NZB and (NZB x NZW)F(1) mice, which normally carry large amounts of Gross virus, and C57BL/6 and NZW mice, which normally carry little virus, were infected with LCM virus. All had Gross soluble antigen in their plasmas at 3 months of age, while noninfected matched controls of all strains did not. This effect was seen after infection with LCM virus that was tissue passed or plaque purified. Similarly, cultures of mouse-embryo fibroblasts produced Gross soluble antigen when infected with LCM virus, but noninfected cultures failed to do so.     

Identification of a cellular cofactor required for infection by feline leukemia virus

Retroviral infection involves continued genetic variation, leading to phenotypic and immunological selection for more fit virus variants in the host. For retroviruses that cause immunodeficiency, pathogenesis is linked to the emergence of T cell-tropic, cytopathic viruses. Here we show that an immunodeficiency-inducing, T cell-tropic feline leukemia virus (FeLV) has evolved such that it cannot infect cells unless both a classic multiple membrane-spanning receptor molecule (Pit1) and a second coreceptor or entry factor are present. This second receptor component, which we call FeLIX, was identified as an endogenously expressed protein that is similar to a portion of the FeLV envelope protein. This cellular protein can function either as a transmembrane protein or as a soluble component to facilitate infection.     

Leukemia virus activation during homograft rejection

Activation of murine leukemia viruses, as detected by the mixed culture cytopathogenicity (XC) assay, followed the transplantation of A/J skin onto immunosuppressed BALB/c mice. Virus was found in most of the mice receiving both skin grafts and antilymphocyte serum, but not in animals receiving either the serum alone, skin graft alone, or no treatment.     

Leukemogenic activity of ether-extracted Rauscher leukemia virus

After rapid multiple extractions of mouse plasma virus with ether, the aqueous solution contained viral nucleoids that were infectious when inoculated intracranially into newborn BALB/c mice. The infectivity associated with the ether extract was not neutralized by the specific antibody prepared against the whole virus. No intact virus has been seen in these preparations. Treatment with ether completely removed the virus envelope from the particle and produced an apparently homogeneous preparation of viral nucleoids. After the extractions with ether, leukemogenic activity was inactivated by exposure to ribonuclease. The leukemogenic activity of the many-passaged Rauscher virus that has been propagated in tissue culture and that has low infectivity was also retained, and, in two experiments in which material was inoculated intracranially into mice, this activity appeared to have been enhanced by multiple extractions with ether.     

Neoplastic transformation of rat thymic cells induced in vitro by Gross leukemia virus

Cultures of embryonal rat thymus infected initially with Gross leukemia virus have, at the present time, abundantly replicated infectious virus particles for 20 months. Cells from these cultures, after 3 months in vitro, displayed morphological changes and induced formation of tumors upon isotransplantation. The tumors were serially transplantable, and subsequent transplants continue to carry the initial Gross leukemia virus.     

Resistance of mice infected with Moloney leukemia virus to Friend virus infection

Mice inoculated with the Moloney strain of mouse lymphoid-leukemia virus showed marked diminution of spleen weight response to infection with Friend leukemia virus given 3 to 4 weeks later.     

Radiation leukemia virus: quantitative tissue culture assay

Radiation leukemia virus does not propagate in tissue cultures from either Swiss or C57BL mouse embryos, but it does augment focus formation by the defective Moloney leukemia pseudotype of murine sarcoma virus in Swiss mouse cells and thus can be quantitatively assayed.     

Phagocytes as carcinogens: malignant transformation produced by human neutrophils

In a study of the relation between chronic inflammation and carcinogenesis, C3H mouse fibroblasts of the 10T 1/2 clone 8 line (10T 1/2 cells) were exposed to human neutrophils stimulated to synthesize reactive oxygen intermediates or to a cell-free enzymatic system generating superoxide (xanthine oxidase plus hypoxanthine). After exposure, the 10T 1/2 cells were either placed in tissue culture or immediately injected into athymic nude mice. Both malignant and benign tumors developed in the mice injected with treated cells, but not in those injected with control cells; in one instance cells grown from one of the benign tumors subsequently developed a malignant phenotype. Malignant transformation was also observed in treated cells in the experiments in vitro.     

不同化学激活方法对山羊卵母细胞激活效果的研究

激活是体细胞核移植技术的关键步骤。本研究对常用化学激活剂乙醇、钙离子载体A2 3187和离子霉素以及添加 6 二甲基氨基嘌呤 (6 Dimethylaminopurine ,6 DMAP)和放线菌酮 (cycloheximide ,CHX)对山羊卵母细胞的激活效果以及不同卵龄的卵母细胞激活后体外发育效果进行了比较。结果表明 :离子霉素处理组激活率显著高于乙醇和A2 3187处理组 (89.6 %vs 6 3.5 % ,6 8.7% ;P <0 .0 5 ) ;离子霉素 +6 -DMAP处理组激活率显著高于离子霉素 +CHX和离子霉素 +CHX +细胞松弛素D处理组 (90 .1%vs 5 8.9% ,6 3.7% ;P <0 .0 1) ;体外成熟 2 4、2 6、2 8h组桑椹胚率分别为 16 .0 %、2 0 .6 %和 33.3% ,30h组桑椹胚率下降 (13.8% )。以上结果说明 ,在本研究的激活条件下 ,山羊卵母细胞适宜的激活方法为 :成熟起始后 2 8h使用离子霉素和 6 DMAP进行联合激活。