Micronuclei, a biomarker for chemoprevention trials: results of a randomized study in oral pre-malignancy.
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.
Benner
S E
SE
Department of Thoracic/Head and Neck Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Lippman
S M
SM
Wargovich
M J
MJ
Lee
J J
JJ
Velasco
M
M
Martin
J W
JW
Toth
B B
BB
Hong
W K
WK
D014408:Biomarkers, Tumor; D002338:Carotenoids / Q000627:therapeutic use; D002471:Cell Transformation, Neoplastic; D005260:Female; D006801:Humans; D015474:Isotretinoin / Q000627:therapeutic use; D007972:Leukoplakia, Oral / Q000188:drug therapy / Q000517:prevention & control / Q000648:ultrastructure*; D008297:Male; D048629:Micronuclei, Chromosome-Defective; D008875:Middle Aged; D009061:Mouth Mucosa / Q000648:ultrastructure; D009062:Mouth Neoplasms / Q000188:drug therapy / Q000517:prevention & control* / Q000648:ultrastructure; D011230:Precancerous Conditions / Q000188:drug therapy / Q000517:prevention & control / Q000648:ultrastructure; D012074:Remission Induction; D018709:Statistics, Nonparametric; D019207:beta Carotene
D014408:Biomarkers, Tumor; D019207:beta Carotene; D002338:Carotenoids; D015474:Isotretinoin