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

Peter H. Bartels, James Ranger-Moore, M. Suzanne Stratton, Paul Bozzo, Janine Einspahr, Yun Liu, Deborah Thompson, David S. Alberts

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


OBJECTIVE: To develop numeric, statistically secured measures of chemopreventive efficacy and to derive procedures with high sensitivity of detection. STUDY DESIGN: 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. CONCLUSION: 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.

Original languageEnglish (US)
Pages (from-to)185-197
Number of pages13
JournalAnalytical and Quantitative Cytology and Histology
Issue number4
StatePublished - Aug 1 2002


  • Actinic keratoses
  • Chemoprevention
  • Computer-assisted
  • Image analysis
  • Keratosis
  • Vitamin A

ASJC Scopus subject areas

  • Anatomy
  • Histology


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