The in vitro cytotoxicity of recombinant human tumor necrosis factor-alpha (rh-TNF-alpha) and actinomycin D (ACT-D) on canine normal and tumor cells was investigated. rh-TNF-alpha showed dose-dependent cytotoxic and cell-growth inhibitory effects on cultured canine kidney carcinoma cells (CKCa-1). rh-TNF-alpha alone produced little cytotoxic effect on canine normal cells. However, combined with ACT-D, it showed moderate cytotoxicity on normal canine cells from the kidney medulla, spleen, heart muscle and lung. When the effects on the spontaneous tumor cells were examined, the combination of rh-TNF-alpha and ACT-D produced substantial cytotoxic effect on 60% of the tumor cells. All mammary mixed tumors and perianal gland tumors tested were susceptible to this combination. The data indicated the combination of rh-TNF-alpha and ACT-D have in vitro cytotoxicity on certain canine tumor cells.

pdf/in-vitro-cytotoxicity-of-recombinant-human-tnf-alpha-and-4icq71bi0q.pdf

In vitro cytotoxicity of recombinant human-TNF-alpha and actinomycin D on canine normal and tumor cells.

Based on the recent findings that show how recombinant human tumor necrosis factor (rh-TNF)-α has potent antitumor activity on human cancer patients when it locally administrated, we have tested the cytotoxicity of rh-TNF-α on 3 canine cultured cells: (1) canine kidney carcinoma (CKCa-1), (2) mastocytoma and (3) Mardin Darby canine kidney cells (MDCK). The cell surface expression of TNF-α receptors on these canine cells was also determined with anti-human TNF RI and RII polyclonal antibodies. Our data shows that on CKCa-1 which has TNF RI receptors rh-TNF-α induced cytotoxicity. By contrast, it exhibited no toxicity on canine mastocytoma which has mainly RII receptors. The data also suggest actinomycin D (ACT-D), an anticancer antibiotic, enhanced the cytotoxicity of rh-TNF-α. Combined with ACT-D, rh-TNF-α showed the cytotoxicity on MDCK which possessed both TNF RI and RII receptors. The results indicate that the cytotoxicity of rh-TNF-α depends on the presence of TNF RI receptors on canine tumor cells.

Cytotoxicity induced by recombinant human tumor necrosis factor-alpha dependent on the types of its receptors on canine cells.

Chemosensitivity of human tumors in vitro evaluated by the succinate dehydrogenase inhibition (SDI) test

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Chemosensitivity of human tumors in vitro evaluated by the succinate dehydrogenase inhibition (SDI) test