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Anal Quant Cytol Histol. 2002 Aug;24(4):185-97.

Statistical analysis of chemopreventive efficacy of vitamin A in sun-exposed, normal skin.

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Optical Sciences Center, University of Arizona, Tucson, USA.



To develop numeric, statistically secured measures of chemopreventive efficacy and to derive procedures with high sensitivity of detection.


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.


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.


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.

[Indexed for MEDLINE]

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