Tumour regression after treatment with aminated beta 1-3D polyglucose is initiated by circulatory failure.

Meth A sarcoma grew progressively when inoculated intradermally in CB6 mice. When the mice were treated on day 7 after inoculation with 10 mg aminated polyglucose (AG) [Bogwald, J., Hoffman, J. & Seljelid, R. Carbohydrate Res. 148, 101, 1986], the tumours regressed completely in over 90% of the cases. During the first hours after AG treatment, tumour thymidine incorporation decreased, adenosine triphosphate (ATP) content decreased, and there were indications of circulatory disturbance as shown by decreased deposition of dye (trypan blue) in the tumour tissue after intravenous injection. Histological examination demonstrated a conspicuous thickening of the walls of small tumour vessels, statis of red blood cells, and perivascular collections of mononuclear cells only hours after AG treatment. In thymectomized animals, where regression does not occur after AG treatment [Seljelid, R. Bioscience Reports 6, 845, 1986], there was no evidence of circulatory failure, no tumour diameter reduction, and no decrease in colouring following intravenous injection of trypan blue. On the basis of these findings, we conclude that the early phase of events after AG treatment leading to tumour regression involves a vascular phenomenon that causes circulatory disturbance and necrosis. The data also indicate that this initial circulatory failure requires the involvement of functional T cells.