Rapid chemosensitivity assay with human normal and tumor cells in vitro.
Neutral red assay, as an index of cytotoxicity, has been applied to predictive screening of chemotherapeutic agents. Human hepatoma and melanoma tumor cells and normal melanocytes, keratinocytes, and fibroblasts were incubated for 2, 24, and 48 h with graded concentrations of cis-platinum (0.1 to 80 microM), doxorubicin (0.01 to 100 microM), and 5-fluorouracil (1 to 1000 microM). Cells were most sensitive after 48 h. Tumor cells, based on 50% toxicity values, were 2-4 times more sensitive than the normal cells, except for cis-platinum, where only melanoma cells, as compared to normal melanocytes, showed a marked difference in cytotoxic response. Methotrexate (1 to 10 microM) toxicity could be reversed in the presence of 100 microM of leucovorin. This sensitive, rapid, and economical assay is suitable for preclinical screening and drug development.
Borenfreund
E
E
Laboratory Animal Research Center, Rockefeller University, New York, New York 10021.
Babich
H
H
Martin-Alguacil
N
N
D000970:Antineoplastic Agents / Q000633:toxicity; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002945:Cisplatin / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000633:toxicity; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D005472:Fluorouracil / Q000633:toxicity; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects; D008113:Liver Neoplasms / Q000473:pathology; D008544:Melanocytes / Q000166:cytology / Q000187:drug effects; D008545:Melanoma / Q000473:pathology; D008727:Methotrexate / Q000633:toxicity; D009499:Neutral Red; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D009499:Neutral Red; D004317:Doxorubicin; D002945:Cisplatin; D005472:Fluorouracil; D008727:Methotrexate