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Characterization of ribonucleolytic activity of angiogenin towards tRNA.

Yeast tRNA is a convenient substrate for the assay of the ribonucleolytic activity of human angiogenin. The optimal pH, [NaCl], and temperature for tRNA cleavage by angiogenin are approximately 6.8, 15-30 mM, and approximately 55 degrees C, respectively, as compared with approximately 8.0, 100-200 mM, and approximately 65 degrees C, respectively, for RNase A. Polyanions and metals both inhibit angiogenin and RNase A but to different extents.

Angiogenesis Inducing Agents↗

Inhibition of HIV-1 proviral DNA synthesis and RNA accumulation by mismatched dsRNA.

The antiviral activity of mismatched dsRNA of the form poly(I):poly(C12-U)n (Ampligen) against the human immunodeficiency virus type 1 (HIV-1) was investigated by RNA-RNA and RNA-DNA hybridizations. Mismatched dsRNA delayed the appearance of newly transcribed HIV-1 RNA as detected by liquid dot-blot hybridization in cultures of H9 T-lymphoblastoid cells following virus challenge. The appearance of proviral DNA as detected by Southern hybridization following virus challenge in H9 cells was also delayed. Mismatched dsRNA had no effect in syncytium inhibition assays performed by fusing MT-2 cells with H9/HTLV-IIIB cells. These results suggest that the in vitro anti-HIV-1 activity of mismatched dsRNA occurs, at least in part, at an early stage in the viral replication cycle following initial gp120-CD4 binding.

Antiviral Agents↗

Supplement-induced cytotoxic cells (SICC) generated from mouse thymus or spleen cells cultured in the presence of interleukin 2 and/or polyinosinic acid.

Mouse thymocytes and spleen cells from unprimed C57BL/6 donors generate broadly reactive cytotoxic cells during 5 days of culture in vitro with polyinosinic acid (5') (poly(I] and/or supernatant from PMA-treated EL4 leukemia cells which contains interleukin 2 (IL-2) activity. We refer here to such cytotoxic cells as "supplement-induced cytotoxic cells" or SICC. Thymocytes are dependent on the supernatant factor(s), whereas spleen cells are usually stimulated by poly(I) alone. Polyinosinic acid acts synergistically with supernatant factor(s) to stimulate generation of SICC by both thymocytes (SICC-T) and spleen cells (SICC-S) when the IL-2 activity of the supernatant is inadequate alone. SICC can be generated by both splenocytes and thymocytes in medium supplemented with fetal calf serum or syngeneic plasma. SICC are active in 4 hr 51Cr-release tests against syngeneic, allogeneic, and xenogeneic tumors but not against lipopolysaccharide-induced lymphoblasts. Embryonic fibroblasts, too, are sensitive to SICC generated by thymocytes. In complement-dependent depletion tests, cytotoxic activity is partially sensitive (SICC-T) or fully sensitive (SICC-S) to anti-Thy-1 and -H-2 but not to anti-Lyt-1, -Lyt-2, or -asialo GM1.

Age Factors↗

The conversion of benzo(alpha)pyrene 4,5-oxide into 4-hydroxybenzo(alpha)pyrene in the presence of polyriboguanylic acid.

Incubation of benzo[alpha] pyrene 4,5-oxide with poly(G) in neutral aqueous ethanol resulted in the formation of covalent adducts and in the production of free 4-hydroxybenzo[alpha]pyrene. This phenol, which was identified by its UV spectral properties and by its chromatographic characteristics, was also formed but at a much slower rate when the epoxide was incubated with DNA or with GMP. Phenol formation was not detected when benzo[alpha]-pyrene 4,5-oxide was incubated for prolonged periods in the presence of poly(A), poly(C) or poly(U) or in the absence of nucleic acid. Formation of 4-hydroxybenzo[alpha] pyrene from the epoxide in the presence of poly(G) was not accompanied by detectable base modifications or by breakage of phosphodiester linkages.

Benzopyrenes↗