Protein accumulation in lethally damaged cells after treatment with cis-dichlorodiammineplatinum (II): lack of temporal correlation between drug effect and inhibition of spheroid volume growth.
Cells of the human cervix carcinoma cell line NHIK 3025 were grown as multicellular spheroids to a mean diameter of 500 microns and treated for 24 h with graded concentrations of cis-DDP. Drug-induced growth delay and survival of clonogenic cells as related to net protein accumulation were detected. It appears that half of the cells have to be killed to produce a detectable growth delay. Although the rate of growth delay is correlated with the rate of cell inactivation, there is no direct proportionality between these two parameters. Spheroid volume growth was inhibited in a reversible manner for cis-DDP concentrations of up to 3 microns and in an irreversible manner for concentrations above 10 microns when treatment was given for 24 h. Although 24 h treatment with 10 microM cis-DDP induced inactivation of more than 99% of the cells as well as almost complete inhibition of cell proliferation, the volume of the spheroids continued to increase for at least 11 days after treatment. Two-parametric coincident recordings of DNA and protein by use of flow cytometry revealed that the protein content per cell continued to increase for several days after termination of the drug treatment. We conclude that the increase in spheroid volume after treatment with high-dose cis-DDP is due to continued protein accumulation in lethally damaged cells.
Nordal
A K
AK
Department of Tissue Culture, Norwegian Radium Hospital, Oslo.
Juul
N O
NO
Pettersen
E O
EO
D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D004273:DNA, Neoplasm / Q000032:analysis / Q000096:biosynthesis; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D011506:Proteins / Q000032:analysis / Q000378:metabolism*
D004273:DNA, Neoplasm; D011506:Proteins; D002945:Cisplatin