Hepatic-mediated elevation and maintenance of metastatic tumor cell glutathione

Metastatic migration of murine L1210 leukemia cells, sensitive and resistant to the antitumor agent L-phenylalanine mustard, from the peritoneal cavity of mice to the liver resulted in a 2-fold elevation in their GSH content. This increase in GSH was accompanied by a corresponding increase in their resistance to the drug. Cell surface binding studies with the non-penetrating disulfide, 6,6'-dithiodinicotinic acid, indicated that both tumors isolated from the liver had a greater than 5-fold elevation in surface sulfhydryls when compared to their ascitic counterparts. These results indicate a role for the hepatic microenvironment in the maintenance of tumor cell GSH, drug responsiveness, and surface sulfhydryls.