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Preclinical screening for drugs effective against 5-fluorouracil-resistant cells with a murine L5178Y cell line in vitro

Journal Article · · JNCI, J. Natl. Cancer Inst.; (United States)
OSTI ID:5546796
A subline of L5178Y cells has been established in vitro that exhibits a fiftyfold order of resistance to 5-fluorouracil (FUra) as compared to that of the parent line. The cytotoxic effects of 24-hour exposures to 23 antitumor drugs and to radiation were compared in the two cell lines. Four patterns of response were identified: 1) Only two drugs, mitomycin C and adriamycin, proved significantly more cytotoxic to FUra-resistant cells. 2) Four other drugs--anguidine, 4'-(9-acridinylamino)-methanesulfon-m-anisidide, melphalan, and quelamycin--showed marginal superiority against resistant cells. 3) X-radiation and the majority of drugs tested--including 5-azacytidine, 1,3-bis(2-chloroethyl)-1-nitrosourea, cisplatin, bleomycin, dibromodulcitol, razoxane, hydroxyurea, methotrexate, teniposide, etoposide, and three experimental agents, metoprine, spirogermanium HCl, and ellipticinum--proved equally cytotoxic to both cell lines. 4) Cross-resistance with FUra was exhibited with vincristine, vindesine, pyrazofurin, and indicine-N-oxide. This experimental system provides a simple method of testing agents for activity against FUra-resistant cells before phase 1 clinical studies.
Research Organization:
Laboratory of Cellular Chemotherapy, Imperial Cancer Research Fund Laboratories, London, England
OSTI ID:
5546796
Journal Information:
JNCI, J. Natl. Cancer Inst.; (United States), Journal Name: JNCI, J. Natl. Cancer Inst.; (United States) Vol. 71:2; ISSN JJIND
Country of Publication:
United States
Language:
English

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Related Subjects

550600* -- Medicine
560121 -- Radiation Effects on Cells-- External Source-- (-1987)
62 RADIOLOGY AND NUCLEAR MEDICINE
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANTI-INFECTIVE AGENTS
ANTIBIOTICS
ANTIMETABOLITES
ANTIMITOTIC DRUGS
ANTINEOPLASTIC DRUGS
AZINES
BLEOMYCIN
CELL CULTURES
COMPARATIVE EVALUATIONS
DOXORUBICIN
DRUGS
ELECTROMAGNETIC RADIATION
FLUOROURACILS
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
IONIZING RADIATIONS
METHOTREXATE
MITOMYCIN
NITROSO COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC FLUORINE COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PYRIMIDINES
RADIATIONS
TOXICITY
URACILS
X RADIATION