Muscle sarcomas and alopecia in A/J mice chronically treated with nicotine.
Muscle sarcomas and alopecia in A/J mice chronically treated with nicotine.
复制标题
DOI：
10.1016/j.lfs.2012.03.041
复制
发表时间：
2012-11-27
期刊：
影响因子：
6.1
通讯作者：
Grando, Sergei A.
中科院分区：
文献类型：
--
作者：
Galitovskiy, Valentin;Chernyavsky, Alexander I.;Edwards, Robert A.;Grando, Sergei A.
目的探讨尼古丁对烟草诱发肺癌易感A/J小鼠长期染毒的病理生物学效应。实验组小鼠皮下注射LD 50剂量的（-）酒石酸氢尼古丁3 mg/kg/天，每周5天，持续24个月，对照组接受磷酸盐缓冲盐水溶剂。尼古丁治疗组小鼠（78.6%）发生子宫或骨骼肌肿瘤，而对照组小鼠无一例发生。子宫肿瘤的检查显示平滑肌瘤，由具有大的深染核的平滑肌样细胞组成。大腿肿瘤的切片显示由丰满的梭形细胞组成的密集细胞肿瘤，偶尔形成“带状”细胞，含有扭曲的条纹。两种肿瘤均为结蛋白染色阳性。在一只尼古丁处理的小鼠中也发生了具有乳头状结构的孤立性肺腺瘤。实验小鼠也出现短暂性脱发，开始为小块脱发，进展为完全脱发的明显局限区域或大面积弥漫性脱发。我们首次证明，慢性尼古丁治疗可以诱导肌肉肉瘤的发展以及短暂的脱发。这些发现可能有助于解释儿童横纹肌肉瘤与父母吸烟和吸烟者早期秃顶的关系。尼古丁的病理生物学效应是否由其受体介导的作用和/或其组织代谢物可替宁和N '-亚硝基去甲尼古丁引起，或由于尼古丁可能的细胞内蓄积而激活的活性氧簇的毒性效应，仍有待确定。
To evaluate the pathobiologic effects of long-term treatment with nicotine of A/J mice susceptible to tobacco-induced lung carcinogenesis. Experimental group of mice received subcutaneous injections of the LD50 dose of (−)nicotine hydrogen tartrate of 3 mg/kg/day, 5 days per week for 24 months, and control group received the vehicle phosphate-buffered saline. Nicotine treated mice, 78.6%, but none of control of mice, developed neoplasms originating from uterus or skeletal muscle. Examination of the uterine neoplasms revealed leiomyosarcomas, composed of whorled bundles of smooth-muscle like cells with large and hyperchromatic nuclei. Sections of the thigh neoplasms revealed densely cellular tumors composed of plump spindle cells, with occasional formation of ‘strap’ cells, containing distorted striations. Both neoplasms were positive for desmin staining. A solitary pulmonary adenoma with papillary architecture also occurred in one nicotine treated mouse. Experimental mice also developed transient balding starting as small patches of alopecia that progressed to distinct circumscribed areas of complete hair loss or large areas of diffuse hair loss. We demonstrate for the first time that chronic nicotine treatment can induce the development of muscle sarcomas as well as transient hair loss. These findings may help explain the association of childhood rhabdomyosarcoma with parental smoking and earlier onset of balding in smokers. It remains to be determined whether the pathobiologic effects of nicotine result from its receptor mediated action and/or its tissue metabolites cotinine and N'-nitrosonornicotine, or toxic effects of reactive oxygen species activated due to possible intracellular accumulation of nicotine.
登录
查看更多内容
影响因子：
6.1
作者：
Waldum, HL;Nilsen, OG;Brenna, E
通讯作者：
Brenna, E
影响因子：
4.7
作者：
Witschi, H;Espiritu, I;Jones, AD
通讯作者：
Jones, AD
影响因子：
3.8
作者：
Nair, MK;Chetty, DJ;Chien, YW
通讯作者：
Chien, YW
影响因子：
4.7
作者：
Stepanov, Irina;Carmella, Steven G.;Hecht, Stephen S.
通讯作者：
Hecht, Stephen S.
影响因子：
--
作者：
Shimkin, M B;Stoner, G D
通讯作者：
Stoner, G D