title: Cytotoxic effects of anticancer agents on subconfluent and multilayered postconfluent cultures.
abstract: The cytotoxic effects of conventional (doxorubicin, 5-fluorouracil, cisplatin) and investigational (2',2'-difluorodeoxycytidine, hexadecylphosphocholine, EO9, rhizoxin) anticancer drugs were studied in subconfluent and multilayered postconfluent cultures of human colon and ovarian carcinoma cell lines. Chemosensitivity was assessed 4 days after a 24-h drug exposure with the sulphorhodamine B assay. Except for rhizoxin, all drugs tested yielded an EC50 (drug concentration producing absorbance readings 50% lower than those of non-treated wells) in postconfluent cultures that were higher than an EC50 obtained with subconfluent cultures. Compared with subconfluent cultures, postconfluent cultures showed decreased cellular nucleotide concentrations and ATP/ADP ratios, in addition to an increased percentage of G0/G1 cells. The activity of DT-diaphorase, a reductase involved in the bioactivation of EO9, was similar in sub- and postconfluent cultures. These results indicate similarity of the postconfluent model presented with those obtained with in vivo models and more complex in vitro techniques.
authors.affiliation: Department of Oncology, Free University Hospital, Amsterdam, The Netherlands.
authors.forename: P E
authors.initials: PE
authors.lastname: Pizao
authors.forename: G J
authors.initials: GJ
authors.lastname: Peters
authors.forename: J
authors.initials: J
authors.lastname: Van Ark-Otte
authors.forename: L A
authors.initials: LA
authors.lastname: Smets
authors.forename: E
authors.initials: E
authors.lastname: Smitskamp-Wilms
authors.forename: B
authors.initials: B
authors.lastname: Winograd
authors.forename: H M
authors.initials: HM
authors.lastname: Pinedo
authors.forename: G
authors.initials: G
authors.lastname: Giaccone
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002453:Cell Cycle; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D016660:NAD(P)H Dehydrogenase (Quinone)