Measuring cytotoxicity: a new perspective on LC50.
BACKGROUND
Cytotoxicity in cell culture is typically expressed as LC50 the concentration of a given agent which is lethal to 50% of the cells. This number is dependent on the incubation time with the agent. Previously, a two-term exponential model has been proposed to describe cell growth after a cytotoxic event: y(t) = k, * exp(-d(1)*t) + k2 * exp(d(2)*t). A dose-response relationship was observed between the parameter k2 in this formula and the concentration of the cytotoxic agent etoposide, in high-grade glioma cells was independent of incubation time.


METHODS
In order to test if the model can be applied more generally, DAOY medulloblastoma cells treated with MS275, a histone deacetylase inhibitor, were used.


RESULTS
The observed data fit the model well.


CONCLUSIONS
The concentration at which k2 is reduced by 50% is called KC50. It provides a far better description of the cytotoxicity of an agent in a specific cell line than the traditional LC50.
Zhang
Ming
M
Department of Bioinformatics and Computational Biology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Aguilera
Dolly
D
Das
Chandra
C
Vasquez
Hernan
H
Zage
Peter
P
Gopalakrishnan
Vidya
V
Wolff
Johannes
J
D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D001549:Benzamides / Q000493:pharmacokinetics / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D006801:Humans; D008297:Male; D008527:Medulloblastoma / Q000188:drug therapy* / Q000378:metabolism; D008954:Models, Biological; D011725:Pyridines / Q000493:pharmacokinetics / Q000494:pharmacology*
D000970:Antineoplastic Agents; D001549:Benzamides; D011725:Pyridines; C118739:entinostat