Micronuclei, a biomarker for chemoprevention trials: results of a randomized study in oral pre-malignancy

Int J Cancer. 1994 Nov 15;59(4):457-9. doi: 10.1002/ijc.2910590403.


Biomarkers are being sought that could serve as surrogate end points for chemoprevention trials. Micronuclei, cytoplasmic fragments of DNA, have been proposed as a biomarker and studied in oral pre-malignancy. This study evaluated micronuclei frequency in a randomized chemoprevention trial of oral pre-malignancy. A recent clinical trial evaluated the responses of pre-malignant oral lesions to 3 months of therapy with isotretinoin followed by 9 months of either low-dose isotretinoin or beta-carotene. For 57 study participants, micronuclei were counted in mucosal scrapings of the lesion and in normal-appearing mucosa at baseline and following 3 months and 12 months of therapy. Micronuclei counts were higher in scrapings from the lesion than in the normal-appearing mucosa. Following 3 months of isotretinoin, the micronuclei counts in scrapings of the lesion were significantly reduced. With treatment, the mean micronuclei count declined at 3 months. In a randomized comparison, both isotretinoin and beta-carotene maintained the suppression of micronuclei. The change in micronuclei count was not associated with the clinical or histological response to treatment. Chemoprevention treatment with isotretinoin led to a reduction in frequency of micronuclei, a marker of recent DNA injury, which was then maintained by both isotretinoin and beta-carotene.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Biomarkers, Tumor*
  • Carotenoids / therapeutic use
  • Cell Transformation, Neoplastic
  • Female
  • Humans
  • Isotretinoin / therapeutic use
  • Leukoplakia, Oral / drug therapy
  • Leukoplakia, Oral / prevention & control
  • Leukoplakia, Oral / ultrastructure*
  • Male
  • Micronuclei, Chromosome-Defective*
  • Middle Aged
  • Mouth Mucosa / ultrastructure
  • Mouth Neoplasms / drug therapy
  • Mouth Neoplasms / prevention & control*
  • Mouth Neoplasms / ultrastructure
  • Precancerous Conditions / drug therapy
  • Precancerous Conditions / prevention & control
  • Precancerous Conditions / ultrastructure
  • Remission Induction
  • Statistics, Nonparametric
  • beta Carotene


  • Biomarkers, Tumor
  • beta Carotene
  • Carotenoids
  • Isotretinoin