Influence of chemotherapeutic agents on chorionic gonadotropin-alpha subunit secretion in a human lung cancer cell line (ChaGo): discordance of cytotoxic and secretory effects.
Cells from cultures of ChaGo, a cell line of a human lung cancer that ectopically produces chorionic gonadotropin (hCG) and its alpha subunit (hCG-alpha) were exposed to five different cancer chemotherapeutic agents in vitro in separate experiments (one drug/expt). The control doubling time averaged 4 days, with molar biphasic secretory rates of hCG-alpha ranging from a high of 58.1 to a low of 10.5 pmoles/10(6) cells/24 hours. Drug concentrations were chosen to induce a 30-60% inhibition of cell replication over a period of 8-10 days. Neither methotrexate nor vincristine demonstrated major effects on extracellular hCG-alpha production, but each agent moderately depressed cell number and each produced major inhibition of intracellular protein synthesis. Procarbazine inhibited marker production only in slight excess of inhibition of cell growth and cell protein. Actinomycin D and mechlorethamine, however, had profound effects on inhibition of hCG-alpha production in excess of cell growth. Our results indicated that cancer chemotherapeutic agents have specific and differing effects on cell growth and cell protein on the one hand and marker production on the other. These data suggested a mechanism for certain cases of discordance between hormone production and clinical status.
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D006063:Chorionic Gonadotropin / Q000378:metabolism*; D003609:Dactinomycin / Q000494:pharmacology; D006729:Hormones, Ectopic / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008466:Mechlorethamine / Q000494:pharmacology; D008727:Methotrexate / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000096:biosynthesis; D009374:Neoplasms, Experimental / Q000378:metabolism; D011344:Procarbazine / Q000494:pharmacology; D014750:Vincristine / Q000494:pharmacology
D000970:Antineoplastic Agents; D006063:Chorionic Gonadotropin; D006729:Hormones, Ectopic; D009363:Neoplasm Proteins; D003609:Dactinomycin; D011344:Procarbazine; D008466:Mechlorethamine; D014750:Vincristine; D008727:Methotrexate