Abstract
When various synthetic double‐ or single‐stranded DNAs were incubated with spleen cells from mice (BALB/c or CDF1) at 37° for 20 hr, it was found that some of the DNAs augmented NK activity and produced factors in the culture supernatants which showed antiviral activity and activity to render mouse macrophages cytotoxic toward tumor cells. Poly(dG, dC) showed the strongest activities, when incubated with spleen cells from lipopolysaccharide‐nonresponsive mice, C3H/HeJ. The activity of the culture supernatant to activate macrophages was completely abolished by a small amount of anti‐IFNγ antibody. On the other hand, the virus‐inhibitory activity of the supernatant was mostly neutralized by anti‐IFNα/β. When IMC tumor cells (5 × 105 cells) were mixed with poly(dG, dC) (100 μg) and then inoculated intradermally into CDF1 mice, the tumor did not take, while tumors grew progressively and killed the mice in a control group inoculated with tumor cells alone. Direct cytotoxicity of poly(dG, dC) at a concentration of 1,000 μg/ml against IMC cells was not observed in vitro.
Keywords: Interferon, Macrophage activating factor, Natural killer cells, Synthetic single‐stranded DNA, Polydeoxyriboguanylic, deoxy‐ribocytidylic acid
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REFERENCES
- 1. ) Lampson , G. P. , Tytell , A. A. , Field , A. K. , Nemes , M. M. and Hilleman , M. R.Inducers of interferon and host resistance, I. Double‐stranded RNA from extracts of Penicillium funiculosum . Proc. Natl. Acad. Sci. USA , 58 , 782 – 789 ( 1967. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2. ) Lampson , G. P. , Field , A. K. , Tytell , A. A. , Nemes , M. M. and Hilleman , M. R.Relationship of molecular size of rIn:rCn (poly I: C) to induction of interferon and host resistance . Proc. Soc. Exp. Biol. Med. , 135 , 911 – 918 ( 1970. ). [DOI] [PubMed] [Google Scholar]
- 3. ) Colby , C. and Chamberlin , M. J.The specificity of interferon induction in chick embryo cells by helical RNA . Proc. Natl. Acad. Sci. USA , 63 , 160 – 167 ( 1969. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4. ) Colby , C.The induction of interferon by natural and synthetic polynucleotides . Prog. Nucleic Acid Res. Mol. Biol. , 11 , 1 – 32 ( 1971. ). [DOI] [PubMed] [Google Scholar]
- 5. ) De Clercq , Eckstein , F. and Merigan , T. C.Structural requirements for synthetic polyanions to act as interferon inducers . Ann. NY Acad. Sci. , 173 , 444 – 461 ( 1970. ). [Google Scholar]
- 6. ) Tokunaga , T. , Yamamoto , H. , Shimada , S. , Abe , H. , Fukuda T. , Fujisawa , Y. , Furutani , Y. , Yano , O. , Kataoka , T. , Sudo , T. , Makiguchi , N. and Suganuma , T.Antitumor activity of deoxyribonucleic acid fraction from Mycobacterium bovis BCG. I. Isolation, physicochemical characterization, and anti‐tumor activity . J. Natl. Cancer Inst. , 72 , 955 – 962 ( 1984. ). [PubMed] [Google Scholar]
- 7. ) Shimada , S. , Yano , O. , Inoue , H. , Kuramoto , E. , Fukuda , T. , Yamamoto , H. , Kataoka , T. and Tokunaga , T.Antitumor activity of the DNA fraction from Mycobacterium bovis BCG. II. Effects on various syngeneic mouse tumors . J. Natl. Cancer Inst. , 74 , 681 – 689 ( 1985. ). [PubMed] [Google Scholar]
- 8. ) Shimada , S. , Yano , O. and Tokunaga , T.In vivo augmentation of natural killer cell activity with a deoxyribonucleic acid fraction of BCG . Jpn. J. Cancer Res. (Gann) , 77 , 808 – 816 ( 1986. ). [PubMed] [Google Scholar]
- 9. ) Yamamoto , S. , Kuramoto , E. , Shimada , S. and Tokunaga , T.In vitro augmentation of natural killer cell activity and production of interferon‐α/β and ‐γ with deoxyribonucleic acid fraction from Mycobacterium bovis BCG . Jpn. J. Cancer Res. (Gann) , 79 ( 1988. ), in press . [DOI] [PMC free article] [PubMed] [Google Scholar]