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.
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Ahmad
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Mulberg
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Aljian
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Vistica
D000818:Animals; D004351:Drug Resistance; D005978:Glutathione / Q000032:analysis*; D007939:Leukemia L1210 / Q000188:drug therapy / Q000378:metabolism; D008099:Liver / Q000502:physiology*; D008114:Liver Neoplasms, Experimental / Q000556:secondary; D008297:Male; D008558:Melphalan / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D009374:Neoplasms, Experimental / Q000032:analysis* / Q000188:drug therapy; D009539:Nicotinic Acids / Q000378:metabolism / Q000494:pharmacology; D013438:Sulfhydryl Compounds / Q000502:physiology
D009539:Nicotinic Acids; D013438:Sulfhydryl Compounds; C001102:6,6'-dithiodinicotinic acid; D005978:Glutathione; D008558:Melphalan