Rezazadeh H, Julka P K, Athar M
Department of Medical Elementology and Toxicology, Hamdard University, New Delhi, India.
Skin Pharmacol Appl Skin Physiol. 1998 Mar-Apr;11(2):98-103. doi: 10.1159/000029814.
Reactive oxygen species and free radicals have been implicated in the multistep cutaneous chemical carcinogenesis. Much of the experimental evidence in this regard is indirect and is based on observations that prooxidant status usually enhances and antioxidant treatments generally inhibit tumor yield. Iron overload is known to enhance peroxidative damage and cause oxidative stress. In this study, we report that iron overload augments 12-O-tetradecanoylphorbol-13-acetate (TPA)-mediated cutaneous tumor promotion. Female Swiss mice were subjected to iron overload by injecting 1 mg iron/ mouse/day consecutively for 2 weeks. Tumors were initiated by applying a single dose of 7,12-dimethylbenz(a)anthracene and promoted with twice weekly applications of TPA for 20 weeks and the appearance of first tumor (latency period), percent incidence and number of tumors per mouse were recorded. It has been observed that the level of iron in involved (tumor-bearing) skin was about fourfold higher as compared to uninvolved (non-tumor) skin of iron overload animals and about tenfold higher as compared to the iron level in the skin of normal animals. When compared to the iron-unloaded control group, the iron overload mice showed an increased incidence of tumors. In iron overload animals, the tumors appeared 3 weeks earlier and also the number of tumors per mouse was significantly higher (2.5-fold). These data indicate that iron overload augments TPA-mediated tumor promotion. We propose that oxidative stress generated by iron overload may be responsible for the augmentation of cutaneous tumorigenesis.
活性氧和自由基与皮肤化学致癌的多步骤过程有关。这方面的许多实验证据是间接的，基于这样的观察结果：促氧化状态通常会提高肿瘤发生率，而抗氧化治疗通常会抑制肿瘤发生率。已知铁过载会增强过氧化损伤并导致氧化应激。在本研究中，我们报告铁过载会增强12-氧-十四烷酰佛波醇-13-乙酸酯（TPA）介导的皮肤肿瘤促进作用。雌性瑞士小鼠通过连续2周每天注射1毫克铁/只来造成铁过载。通过单次给予7,12-二甲基苯并(a)蒽启动肿瘤形成，并每周两次涂抹TPA促进肿瘤生长20周，记录首次出现肿瘤的时间（潜伏期）、肿瘤发生率和每只小鼠的肿瘤数量。据观察，铁过载动物的受累（有肿瘤）皮肤中的铁水平比未受累（无肿瘤）皮肤高约四倍，比正常动物皮肤中的铁水平高约十倍。与未加载铁的对照组相比，铁过载小鼠的肿瘤发生率增加。在铁过载动物中，肿瘤出现时间提前3周，每只小鼠的肿瘤数量也显著更高（2.5倍）。这些数据表明铁过载会增强TPA介导的肿瘤促进作用。我们认为铁过载产生的氧化应激可能是皮肤肿瘤发生增加的原因。
