Elmets Craig A, Yusuf Nabiha, Hamza Sate, Iranikakh Nasser, Smith Jeffrey, Volk Andrea L, Skelton Henry, Smith Kathy
Department of Dermatology, The University of Alabama at Birmingham, Birmingham, AL 35294-0009, USA.
Toxicol Appl Pharmacol. 2004 Mar 15;195(3):355-60. doi: 10.1016/j.taap.2003.09.029.
Melanocytic nevi are a common dermatological problem for which there are few in vivo models. It has been postulated that environmental factors contribute to their development. Experiments were therefore conducted to determine whether application of dimethylbenz[a]anthracene (DMBA) to the skin of mice would result in the development of melanocytic nevi. One hundred microliters of a 0.1%, 0.5%, or 1.0% solution of DMBA was applied to the dorsal skin of C3H/HeN mice. The mice were then observed for the appearance of pigmented lesions. Histological examination revealed perifollicular accumulations of nevus cells, which were S-100-protein and HMB-45-positive, confirming their melanocytic origin. Pigmented lesions did not occur in animals treated with vehicle alone. Dose response studies revealed both greater numbers of nevi and lesions with larger diameters as the dose of DMBA was increased from 0.1% to 0.5%. In no instance was an invasive melanoma observed even after 40 weeks. The fact that melanocytic nevi can be produced by topical application of DMBA suggests that xenobiotics may play a previously unrecognized role in the development of this common benign neoplasm. Because this is one of the only animal models for melanocytic nevi, further examination of this model may facilitate identification of the molecular and biochemical mechanisms that lead to the development of pigmented nevi and the factors that promote their evolution into invasive melanomas.
黑素细胞痣是一种常见的皮肤问题，目前几乎没有体内模型。据推测，环境因素会促使其形成。因此，开展了实验以确定将二甲基苯并[a]蒽（DMBA）涂抹于小鼠皮肤是否会导致黑素细胞痣的形成。将100微升0.1%、0.5%或1.0%的DMBA溶液涂抹于C3H/HeN小鼠的背部皮肤。随后观察小鼠是否出现色素沉着病变。组织学检查显示毛囊周围有痣细胞聚集，这些细胞S - 100蛋白和HMB - 45呈阳性，证实了它们的黑素细胞起源。仅用赋形剂处理的动物未出现色素沉着病变。剂量反应研究表明，随着DMBA剂量从0.1%增加到0.5%，痣的数量增多且病变直径增大。即使在40周后，也未观察到侵袭性黑色素瘤。局部应用DMBA可产生黑素细胞痣这一事实表明，外源性物质可能在这种常见良性肿瘤的形成过程中发挥了此前未被认识到的作用。由于这是黑素细胞痣仅有的动物模型之一，对该模型的进一步研究可能有助于确定导致色素痣形成的分子和生化机制，以及促使其演变为侵袭性黑色素瘤的因素。
