Cloos J, Bongers V, Lubsen H, Tobi H, Braakhuis B J, Snow G B
Department of Otolaryngology/Head and Neck Surgery, Amsterdam, The Netherlands.
Cancer Epidemiol Biomarkers Prev. 1996 Nov;5(11):941-4.
The European Organization for Research and Treatment of Cancer multicenter Euroscan trial was set up to prevent the occurrence of second primary tumors in the upper aerodigestive and respiratory tract in patients cured for early stage head and neck squamous cell carcinoma. One randomized group of patients receive daily N-acetylcysteine, an antioxidant that may be protective especially in the early steps of carcinogenesis. Mutagen sensitivity, measured as sensitivity to bleomycin in peripheral blood lymphocytes, has been found to be increased in head and neck squamous cell carcinoma and is hypothesized to reflect cancer susceptibility. The aim of this study was to investigate whether mutagen sensitivity is influenced by oral N-acetylcysteine supplementation and can therefore be used as intermediate end point in chemoprevention. Patients (n = 19) who had various periods of N-acetylcysteine supplementation (600 mg daily for 3-9 months) were analyzed. In addition, a patient group (n = 14) that did not receive N-acetylcysteine supplementation was analyzed for comparison. Our results show no evidence that administration of N-acetylcysteine did influence the mutagen sensitivity level. The only explanatory variable in the analysis of the difference between two samples of one person was the b/c value of the first measurement. Moreover, the variability in these repeated measurements (coefficient of variation of 14%) indicates that additional studies should be performed to minimize this variability and to optimize the testing of mutagen sensitivity to accurately identify individual patients at high risk for the development of multiple primary tumors.
欧洲癌症研究与治疗组织开展了多中心欧洲扫描试验，旨在预防早期头颈部鳞状细胞癌治愈患者在上呼吸道和消化道发生第二原发性肿瘤。一组随机分组的患者每日服用N - 乙酰半胱氨酸，这是一种抗氧化剂，尤其在致癌作用的早期阶段可能具有保护作用。已发现头颈部鳞状细胞癌患者外周血淋巴细胞对博来霉素的敏感性（即诱变敏感性）增加，并推测其反映癌症易感性。本研究的目的是调查口服补充N - 乙酰半胱氨酸是否会影响诱变敏感性，以及因此是否可将其用作化学预防的中间终点。对服用不同时间段N - 乙酰半胱氨酸（每日600毫克，持续3 - 9个月）的患者（n = 19）进行了分析。此外，分析了一组未服用N - 乙酰半胱氨酸的患者（n = 14）作为对照。我们的结果表明，没有证据显示服用N - 乙酰半胱氨酸会影响诱变敏感性水平。对同一个人的两个样本差异进行分析时，唯一的解释变量是首次测量的b/c值。此外，这些重复测量的变异性（变异系数为14%）表明，应开展更多研究以尽量减少这种变异性，并优化诱变敏感性检测，从而准确识别有发生多个原发性肿瘤高风险个体。
