Cytotoxic effects of anticancer agents on subconfluent and multilayered postconfluent cultures.
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.
Pizao
P E
PE
Department of Oncology, Free University Hospital, Amsterdam, The Netherlands.
Peters
G J
GJ
Van Ark-Otte
J
J
Smets
L A
LA
Smitskamp-Wilms
E
E
Winograd
B
B
Pinedo
H M
HM
Giaccone
G
G
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*
D000970:Antineoplastic Agents; D016660:NAD(P)H Dehydrogenase (Quinone)