Benner S E, Lippman S M, Wargovich M J, Lee J J, Velasco M, Martin J W, Toth B B, Hong W K
Department of Thoracic/Head and Neck Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
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.
人们正在寻找可作为化学预防试验替代终点的生物标志物。微核作为DNA的细胞质片段，已被提议作为一种生物标志物，并在口腔癌前病变中进行了研究。本研究在一项口腔癌前病变的随机化学预防试验中评估了微核频率。最近的一项临床试验评估了癌前口腔病变对异维A酸3个月治疗以及随后9个月低剂量异维A酸或β-胡萝卜素治疗的反应。对于57名研究参与者，在基线时以及治疗3个月和12个月后，对病变部位的黏膜刮片和外观正常的黏膜中的微核进行计数。病变部位刮片中的微核计数高于外观正常的黏膜。异维A酸治疗3个月后，病变部位刮片中的微核计数显著降低。随着治疗，微核平均计数在3个月时下降。在一项随机比较中，异维A酸和β-胡萝卜素均维持了对微核的抑制作用。微核计数的变化与治疗的临床或组织学反应无关。异维A酸化学预防治疗导致微核频率降低，微核是近期DNA损伤的标志物，随后异维A酸和β-胡萝卜素均维持了这种降低。
