Growth state-specific responsiveness of primary cultures of a nude mouse-xenografted human colon carcinoma to 4'-deoxydoxorubicin and a crude human leukocyte alpha-interferon preparation.
Improved procedures for the seeding of primary cultures from human colon tumors are described. Responsiveness of primary cultures from human colon carcinoma T348 to a crude preparation of human leukocyte alpha-interferon and a DNA-intercalating experimental anticancer drug, 4'-deoxydoxorubicin, has been investigated. The effect of the interferon preparation on such cultures is shown to be growth state specific; i.e., stationary populations are killed, whereas fast-growing cultures are reversibly growth inhibited by the same doses of interferon. In contrast, 4'-deoxydoxorubicin kills growing populations, whereas stationary cultures are barely affected by the same concentration of this drug. Interferon antagonizes the cytotoxic effect of 4'-deoxydoxorubicin on a growing colon tumor cell population when applied immediately after 4'-deoxydoxorubicin treatment. Implications of this finding for the combined application of several drugs in cancer therapy are discussed.
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003110:Colonic Neoplasms / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004347:Drug Interactions; D006801:Humans; D007372:Interferons / Q000494:pharmacology*; D007399:Interphase / Q000187:drug effects; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014183:Transplantation, Heterologous
D004317:Doxorubicin; D007372:Interferons; C030851:esorubicin