In vitro chemopreventive efficacy screening using human keratinocytes and the in vivo data correlation.
Agents with potential cancer preventive activity were screened for efficacy in the Human Epidermal Cell (HEC) Assay. The HEC Assay measures inhibition of propane sultone-induced changes in the growth and/or differentiation in early passage keratinocyte cultures. The assay biomarkers were calcium tolerance, growth inhibition, and involucrin induction. The HEC Assay also provides information on the cytotoxicity of the agents following acute and chronic exposure. Agents were evaluated at non-toxic doses in the HEC Assay. The HEC Assay has been used to screen twenty-eight agents for chemopreventive efficacy. A positive response in one or more endpoints of the HEC Assay correlates 100% (16/16) with a positive response in one or more of the animal cancer prevention models (J. Cell. Biochem., 26S:29-53, 1996). The overall sensitivity for predicting efficacy in animals is 84%. The available data suggest that a positive assay response appears to be highly predictive of efficacy in vivo.
Elmore
E
E
Department of Radiation Oncology, University of California, Irvine 92697, USA.
Sun
C
C
Li
H R
HR
Wyatt
G P
GP
Buckmeier
J A
JA
Steele
V E
VE
Kelloff
G J
GJ
Redpath
J L
JL
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D011498:Protein Precursors / Q000096:biosynthesis
D016588:Anticarcinogenic Agents; D011498:Protein Precursors; C032253:involucrin; D002118:Calcium