Local induction of a cytotoxic factor in a murine tumour by systemic administration of an antitumour polysaccharide, MGA.
When an antitumour mannoglucan prepared from Microellobosporia grisea, MGA was administered i.v. to C3H/He mice bearing the solid MH134 hepatoma, a cytotoxic factor was induced that was detectable in the tumour homogenate by an 8 h cytolysis assay against L-929 fibroblasts. Without MGA treatment, the cytotoxic factor was not detectable in the tumour homogenate. MGA induced the cytotoxic factor in tumour tissue specifically, its level reaching a maximum (24 U ml-1) 3 h after administration of MGA: little if any cytotoxic factor was detectable in homogenates of normal tissues or sera after MGA-treatment. The molecular size of the cytotoxic factor was estimated to be 70-80 kD by gel filtration. It seemed to be a type of tumour necrosis factor because its activity was inhibited by antiserum against murine tumour necrosis factor. From these results, the selective induction of the cytotoxic factor was concluded to be important in the mechanism of the antitumour activity of MGA.
Takahashi
K
K
Research Development Corporation of Japan, Tokyo.
Watanuki
Y
Y
Yamazaki
M
M
Abe
S
S
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002850:Chromatography, Gel; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects; D005936:Glucans / Q000494:pharmacology*; D008114:Liver Neoplasms, Experimental / Q000378:metabolism*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D011135:Polysaccharides, Bacterial / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis*
D000903:Antibiotics, Antineoplastic; D005936:Glucans; C063114:Microellobosporia griesea polyalcoholized mannoglucan; D011135:Polysaccharides, Bacterial; D014409:Tumor Necrosis Factor-alpha