Local induction of a cytotoxic factor in a murine tumour by systemic administration of an antitumour polysaccharide, MGA

K Takahashi,M Yamazaki,Y Watanuki,S Abe

doi:10.1038/bjc.1988.35

Abstract

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.

Highlights

Following MGA treatment, the blood circulation in tumour tissues is inhibited within 6 h (Abe et al, 1985) and tumour growth retarded within 3 days (Abe et al, 1984)
This similarity suggested that the cytotoxic factor (CF) in tumour tissues and TNF might have similar cytotoxic activity
To examine the recovery of the CF during sample preparation, a known quantity (170 units) of murine-TNF was added to the tumour tissues before their homogenization and the cytotoxic activity in the final supernatants measured

Summary

Methods

Inbred male C3H/He mice were purchased from Shizuoka Agricultural Cooperative Association for Laboratory Animals, Hamamatsu. They were 7-9 weeks old at the beginning of the experiments. MH 134, a transplantable ascites hepatoma, was passaged weekly in the peritoneal cavity of C3H/He mice. Wt x 102 kD) was kindly provided by Daiichi Seiyaku Co., Ltd., Tokyo. Lipopolysaccharide (LPS) from E. coli 0127, B8 was purchased from Difco Lab. (Detroit, Mich.), Rabbit (Ruff et al, 1980) and mouse (Carswell et al, 1975) tumour necrosis ser-um (TNS) was prepared as described previously. Takahashi Received 12 June 1987; and in revised form, 24 September 1987

Results

Discussion

Conclusion