Carter Charleata A, Misra Manoj
A. W. Spears Research Center, Lorillard Tobacco Company, Greensboro, North Carolina 27405, USA.
Toxicol Pathol. 2010 Apr;38(3):402-15. doi: 10.1177/0192623310364028. Epub 2010 Mar 9.
A short-term 5-day cigarette smoke exposure study was conducted in Fischer 344 rats to identify smoke-induced lung protein changes. Groups of 10 male and 10 female rats at 5 weeks of age were randomly assigned to one of four exposure groups. Animals received filtered air (control) or 75, 200, or 400 mg total particulate matter (TPM)/m(3) of diluted Kentucky reference 3R4F cigarette smoke. Nose-only exposures were conducted for 3 hours/day for 5 consecutive days. Mean body weights were significantly reduced only in male rats exposed to 400 mg TPM/m(3). Body weight gains were significantly reduced in 200- and 400-mg TPM/m(3)-exposed males and in all smoke-exposed females compared with controls. Alveolar histiocytosis increased slightly in all smoke exposed-females and 200- and 400-mg TPM/m(3)-exposed males. Cyclooxygenase-2 staining increased at 400 mg TPM/m(3). Matrix metalloproteinase-12 staining of alveolar macrophages and bronchiolar epithelia increased in smoke-exposed animals, especially 400-mg TPM/m(3)-exposed females. Protein kinase C-alpha staining increased in macrophages at 200- and 400-mg TPM/m(3) doses. c-Jun NH(2)-terminal kinases staining decreased in smoke-exposed tissues. The identified changed proteins play roles in inflammation, transformation, proliferation, stress activation, and apoptosis.
在Fischer 344大鼠中进行了一项为期5天的短期香烟烟雾暴露研究,以确定烟雾诱导的肺蛋白变化。将10只5周龄的雄性大鼠和10只5周龄的雌性大鼠分为四组,随机分配到四个暴露组之一。动物接受过滤空气(对照组)或75、200或400毫克总颗粒物(TPM)/立方米的稀释肯塔基参考3R4F香烟烟雾。每天仅经鼻暴露3小时,连续暴露5天。仅在暴露于400毫克TPM/立方米的雄性大鼠中,平均体重显著降低。与对照组相比,暴露于200和400毫克TPM/立方米的雄性大鼠以及所有暴露于烟雾的雌性大鼠的体重增加显著减少。所有暴露于烟雾的雌性大鼠以及暴露于200和400毫克TPM/立方米的雄性大鼠的肺泡组织细胞增多症略有增加。在400毫克TPM/立方米时,环氧合酶-2染色增加。在暴露于烟雾的动物中,尤其是暴露于400毫克TPM/立方米的雌性动物中,肺泡巨噬细胞和细支气管上皮细胞的基质金属蛋白酶-12染色增加。在200和400毫克TPM/立方米剂量下,蛋白激酶C-α在巨噬细胞中的染色增加。在暴露于烟雾的组织中,c-Jun NH2末端激酶染色减少。鉴定出的变化蛋白在炎症、转化、增殖、应激激活和细胞凋亡中起作用。