Abstract
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 normalappearing 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. © 1994 Wiley‐Liss, Inc.