The lung tumor promoter, butylated hydroxytoluene (BHT), causes chronic inflammation in promotion-sensitive BALB/cByJ mice but not in promotion-resistant CXB4 mice
The lung tumor promoter, butylated hydroxytoluene (BHT), causes chronic inflammation in promotion-sensitive BALB/cByJ mice but not in promotion-resistant CXB4 mice
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DOI：
10.1016/s0300-483x(01)00475-9
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发表时间：
2001-12-01
期刊：
影响因子：
4.5
通讯作者：
Malkinson, AM
中科院分区：
文献类型：
--
作者：
Bauer, AK;Dwyer-Nield, LD;Malkinson, AM
炎症反应伴随着由丁基羟基甲苯（BHT）给药引起的可逆性肺毒性。在BALB/cByJ小鼠中，在起始剂后给予BHT可促进肺肿瘤的形成，而在CXB4小鼠中则无此作用。为了评估炎症对这种差异易感性的贡献，我们定量地描述了两种品系的雄性小鼠在一次150 mg/kg体重注射BHT后的炎症，随后每周三次注射200 mg/kg体重的BHT。检查包括支气管肺泡灌洗液（BAL）中炎症细胞浸润和蛋白含量，肺提取物中环氧化酶(COX)-1和COX-2的表达，分离的细支气管Clara细胞PGE(2)和PGI(2)的产生。BALB小鼠BAL巨噬细胞和淋巴细胞数量增加（P < 0.0007和0.02），BAL蛋白含量增加（P < 0.05）， COX-1和COX-2表达增加（P < 0.05）， PGI(2)产生增加（P < 0.05）；相反，这些指标在CXB4小鼠中不受BHT的干扰。BALB小鼠在BHT治疗前给予阿司匹林（400mg /kg）两周，炎症细胞浸润减少。我们的研究结果支持了一种假设，即CXB4小鼠对BHT诱导的炎症的抵抗力至少在一定程度上解释了BHT对该菌株肺肿瘤多样性缺乏影响的原因。(C) 2001爱思唯尔科学爱尔兰有限公司版权所有。
An inflammatory response accompanies the reversible pneumotoxicity caused by butylated hydroxytoluene (BHT) administration to mice. Lung tumor formation is promoted by BHT administration following an initiating agent in BALB/cByJ mice, but not in CXB4 mice. To assess the contribution of inflammation to this differential susceptibility, we quantitatively characterized inflammation after one 150 mg/kg body weight, followed by three weekly 200 mg/kg ip injections of BHT into male mice of both strains. This examination included inflammatory cell infiltrate and protein contents in bronchoalveolar lavage (BAL) fluid, cyclooxygenase (COX)-1 and COX-2 expression in lung extracts, and PGE(2) and PGI(2) production by isolated bronchiolar Clara cells. BAL macrophage and lymphocyte numbers increased in BALB mice (P < 0.0007 and 0.02, respectively), as did BAL protein content (P < 0.05), COX-1 and COX-2 expression (P < 0.05 for each), and PGI(2) production (P < 0.05); conversely, these indices were not perturbed by BHT in CXB4 mice. BALB mice fed aspirin (400 mg/kg of chow) for two weeks prior to BHT treatment had reduced inflammatory cell infiltration. Our results support a hypothesis that resistance to BHT-induced inflammation in CXB4 mice accounts, at least in part, for the lack of effect of BHT on lung tumor multiplicity in this strain. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.