Specific genes can be introduced into cultured mammalian cells by DNA transfer, sometimes to be stably integrated and expressed. Because interferon inhibits the transformation initiated by DNA viruses, we wondered if it might also affect transformation induced by recombinant plasmids and cellular genes. We show here that in mouse L cells interferon treatment prevents stable integration and expression of the transfected plasmids containing the cloned herpesvirus thymidine kinase (tk) gene, or the dihydrofolate reductase (dhfr) gene from hamster ovary cells. In contrast, interferon does not prevent transient expression of the tk gene in unintegrated form.

Animals↗

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Cell fusion in viral diseases.

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Animals↗

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Evaluation of poly(styrene-4-sulfonate) as a preventive agent for conception and sexually transmitted diseases.

A commercial preparation of a sodium polystyrene sulfonate (designated as N-PSS; its molecular weight is 500000 daltons) was tested as an inhibitor of sperm function and as a preventive agent for conception and the transmission of sexually transmitted diseases. The polymer is an irreversible inhibitor of hyaluronidase and acrosin; its IC50 values are 5.7 microg/mL and 0.5 microg/mL, for hyaluronidase and acrosin, respectively. N-PSS is also a stimulus of human sperm acrosomal loss. It produces maximal acrosomal loss at 2.5 microg/mL. Contraception in rabbits is nearly complete when rabbit spermatozoa are pretreated with 0.5 mg/mL of N-PSS before artificial insemination; however, N-PSS does not immobilize spermatozoa at concentrations as high as 50 mg/mL. N-PSS has broad spectrum antiviral and antibacterial activities. Infection by human immunodeficiency virus and herpes simplex virus are inhibited by N-PSS; 3-log reductions are produced by 7 microg/mL and 3 microg/mL, respectively. N-PSS is active against Chlamydia trachomatis and Neisseria gonorrhoeae. At 1 mg/mL, N-PSS inhibits chlamydial infectivity by more than 90%. N-PSS produces a 3-log reduction in gonococcal growth at 15 microg/mL. In contrast, N-PSS (5 mg/mL) does not affect the growth of Lactobacillus (normal component of the vaginal flora). N-PSS can be classified as a noncytotoxic contraceptive antimicrobial agent. These properties justify bringing a polystyrene sulfonate into clinical trials for its evaluation as a preventive agent for conception and several sexually transmitted diseases.

Animals↗

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Low level toxicity and antitumor activity of butyric mono- and polyester monosaccharide derivates in mice.

This study compares the antitumor activity of five mono- and polyesters of n-butyric acid derived from monosaccharides in the murine model of Crocker 180 TG Sarcoma. Tumor incidence at ten days, mean survival time and final survival rate were significantly affected in all cases. Combined treatment by butyric esters, alpha/beta interferon (IFN) and/or Corynebacterium parvum used as immunestimulator improved the antitumor protection. Studies of acute toxicity in mice, performed by i.p. and oral routes, showed the low toxicity of butyric esters, which were devoid of detectable side effects with no incidence on ponderal growth when administered per os in rats daily for one month. Finally, a comparative study of antitumor activity, toxicity and water-solubility of various butyric esters enabled us to select among these new molecules two isomers (carbon-3 and carbon-6 of the glucose ring substituted with n-butyric acid) derived from monoacetone glucose for further investigations of their biological mechanism in vivo and in vitro.

Animals↗

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Immunomodulatory effects of arginine butyrate.

We have studied the effect of arginine butyrate on T cell and macrophage functions. When target cells are treated with this substance, they become resistant to T cell-mediated cytotoxicity, as detected by the chromium assay. In contrast, when effector T cells are treated, the cytotoxicity seems to be augmented. Peritoneal macrophages incubated with butyrate are increasingly adhesive to substrate. After in vivo treatment, spleen derived macrophages show an augmented cytostatic capacity in the presence of L1210 cells and an enhanced phagocytic activity for IgG-coated erythrocytes. To sum up, the overall effects of butyrate salts on different immune functions are somewhat reminiscent of that of interferon. It is likely that these immune effects contribute, at least in part, to explain its antitumor properties observed in grafted tumors in mice.

Adjuvants, Immunologic↗

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An experimental and clinical study of immunocompetence and immunostimulation in breast cancer.

Two hundred and seven patients aged from 37 to 65 years with noninflammatory breast cancer treated by surgery without radiation were studied over a ten year period with a view to forecasting the prognosis on the basis of the immune status and treatment. The immunocompetence or immune status was studied in 121 patients by in vitro and in vivo pre and post-surgical skin tests. The immunostimulation or restoration of the immune status was conducted by the P 40 immunomodulator from the Pasteur Institute: in an experimental study whose results are based on modified Huggins model and take in to account the survival rate and the evaluation of tumor growth; in a subgroup of 86 patients, demonstrating that immunostimulation is effective in low-scores, improves tolerance to chemotherapy and increases the six year survival rate in high risk low-score patients. The results are encouraging enough to propose improving the survival rate in a prospective clinical study of early breast cancer treated by local and regional means using a protocol incorporating an immunostimulation based on the existing immunocompetence with interferon-induced reconversion of the target cells in the hope of specific stimulation.

Adjuvants, Immunologic↗

PubMedDate not supplied

[Effect of temperature on the duration of phases of the generation cycle of cells in cultures].

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Culture Techniques↗

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Role of membrane receptors in the biological effects of interferon.

The model of IFN receptor system which we initially proposed in 1973 is now better documented. The receptor system seems to consist of an IFN species specific glycoprotein, which could be the high affinity receptor (30) to which IFN has to bind in order to act. The glycoprotein is thus the activator site. Furthermore, IFN can bind to gangliosides in a non-specific manner. Cooperation between these membrane elements requires the free mobility of the membrane constituents in the plane of the membrane and the integrity of the cytoskeleton. Decay of these constituents during some virus-induced or malignant transformation processes could result in a defect in the synthesis of one of these constituents, causing in parallel a loss of IFN sensitivity. Sodium butyrate, which restores the cytoskeleton, enhances simultaneously the response to IFN. The modulatory effect of IFN on the cell membrane is thus a major step in the regulatory action of IFN on the different phenotypic expressions of the cell. This property of IFN could be one of its principal physiological roles.

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