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Enhancing Effect of Hydrocortisone on Hematogenous Metastasis of Ehrlich Ascites Tumor in Mice¹

Laboratory of Chemotherapy, Aichi Cancer Center Research Institute, Chikusa-ku, Nagoya, Japan

The effect of hydrocortisone on blood-borne tumor metastasis was studied in an i.v. inoculation experiment with Ehrlich hypotetraploid clone 1, Ehrlich hypotetraploid stock, and Ehrlich hyperdiploid stock tumors. The administration of hydrocortisone before tumor inoculation resulted in increased tumor take, reduced mean survival time of mice, and concentration of tumor metastasis in a specific organ (i.e., lung metastasis for Ehrlich hypotetraploid clone 1 tumor, and liver metastasis for Ehrlich hypotetraploid stock and Ehrlich hyperdiploid stock tumors). Enhancement of tumor metastasis, as induced by hydrocortisone pretreatment, was not reproduced by the administration of 6-mercaptopurine, testosterone, or estradiol. The progress of tumor death in hydrocortisone-conditioned mice was not affected by either heparin or dextran sulfate. This indicated that the effect of hydrocortisone on tumor metastasis was independent of the effect of these agents on immune reaction or blood coagulation.

In the tracer experiment with ¹²⁵I-labeled tumor cells, hydrocortisone pretreatment significantly increased over the control the intrapulmonary retention of Ehrlich hypotetraploid clone 1 tumor cells from 1 through 72 hr after tumor inoculation, the time lag required for the establishment of metastatic foci in the lung. The arrest of Ehrlich hypotetraploid stock and Ehrlich hyperdiploid stock tumors in the liver was also temporarily increased by hydrocortisone pretreatment. No correlation was found between tumor cell size and differential distribution of metastatic tumors with 3 Ehrlich tumors.

An attempt was made to use this blood-borne metastasis system for chemotherapeutic study. Administration of cyclophosphamide gave rise to a significant prolongation of survival time and often to complete prevention of tumor metastasis in hydrocortisone-conditioned mice.

¹ Supported in part by a grant for Cancer Research from the Ministry of Education of Japan.

Received 8/19/74. Accepted 11/26/74.

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