Statistical analysis of chemopreventive efficacy of vitamin A in sun-exposed, normal skin.
OBJECTIVE
To develop numeric, statistically secured measures of chemopreventive efficacy and to derive procedures with high sensitivity of detection.


METHODS
Karyometric features were computed for nuclei from the basal cell layer of biopsies taken from sun-exposed but histologically "normal" skin. Biopsies were collected from placebo-treated subjects and subjects treated for one year with daily, oral doses of 25,000, 50,000 and 75,000 IU of vitamin A. A total of 22,600 nuclei were recorded from 113 cases, at baseline and after one year.


RESULTS
Two numeric measures of chemopreventive efficacy were applied: a measure of nuclear abnormality and a measure based on discriminant function scores. Both showed statistically significant chemopreventive effects of vitamin A. Dose-response curves were derived. A novel procedure, second order discriminant analysis, resulted in very high sensitivity for the detection of change in nuclear chromatin patterns.


CONCLUSIONS
Karyometric analysis has increased in sensitivity such that changes on the order of 10%, found in only a low percentage of nuclei in a biopsy specimen, can be reliably documented. The methodology lends itself to cost-efficient screening of compounds for chemopreventive efficacy.
Optical Sciences Center, University of Arizona, Tucson, USA.
Peter H
PH
Bartels
James
J
Ranger-Moore
M Suzanne
MS
Stratton
Paul
P
Bozzo
Janine
J
Einspahr
Yun
Y
Liu
Deborah
D
Thompson
David S
DS
Alberts
D001706:Biopsy; D002467:Cell Nucleus / Q000473:pathology; D003627:Data Interpretation, Statistical; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007642:Keratosis / Q000473:pathology*; D012867:Skin / Q000473:pathology / Q000528:radiation effects*; D013472:Sunlight / Q000009:adverse effects*; D014801:Vitamin A / Q000008:administration & dosage*
D014801:Vitamin A