The effect of cycloheximide, heparin and Ancrod on mice given Ehrlich ascites tumour cells intravenously

Abstract

Mice injected intra-venously with Ehrlich ascites tumour cells showed a fatal susceptibility to normally-tolerated doses of cycloheximide when the latter was given at the following times after the tumour cells—2 h, 24 h, 48 h, and 72 h. When the interval between tumour cell injection and cycloheximide challenge was extended to 1 week or 3 weeks (at which latter time mice have clinical “metastatic” neoplasia), no such susceptibility was shown. In the case of the 2 h interval between tumour cells and cycloheximide (and also when cycloheximide was given 2 h before tumour cells), the lethal syndrome was prevented by heparin treatment and also by Ancrod defibrination. This strongly suggests that heparin is effective by virtue of its anticoagulant properties, and that fibrinogen-to-fibrin conversion is an essential step in the pathogenesis. Neither heparin nor Ancrod confer any protection when used in the syndrome consequent upon cycloheximide challenge 24 h after tumour cell injection, which indicates that, in this case, the conversion of fibrinogen to fibrin is not an essential step in determining the fatal outcome.