Bhattacharyya S N, Manna B, Ashbaugh P, Coutinho R, Kaufman B
Department of Clinical Investigation, William Beaumont Army Medical Center, El Paso, Texas 79920, USA.
Inflammation. 1997 Apr;21(2):133-43. doi: 10.1023/a:1027372618992.
Changes in ultrastructural characteristics and mucin gene expression were examined in rat tracheal explants cultured in a synthetic medium +/- retinoic acid (RA), benzo[a]pyrene (B[a]P) and N-methyl-N-nitrosourea (NMNU). In the RA(+) cultures, no changes in either ultrastructural features or mucin gene expression were detected after 48 h incubation. After 96 h incubation, however, the ultrastructural features associated with the squamous phenotype were characteristics of cultures containing the two carcinogens and the mucin gene expression was slightly reduced. Thus, in the presence of retinoic acid, the carcinogen induced changes in cytology to the squamous phenotypes were not matched by a marked loss of mucin gene expression. Explants cultured for 48 h without RA and +/- carcinogens showed none of the cytological changes associated with onset of the squamous phenotype. While mucin mRNA was still detected, it was clearly reduced compared to 48 h cultures in RA(+) medium. However, 48 h later, all explants exhibited pronounced squamous metaplasia and the mucin message decreased to trace levels. Thus, the results of these experiments with B[a]P and NMNU in RA(+) and RA(-) media indicates that at least the early carcinogen induced changes may be distinct from those associated with the retinoid pathway controlling expression of the mucin component of the mucociliary epithelium.
在添加或不添加视黄酸（RA）、苯并[a]芘（B[a]P）和N-甲基-N-亚硝基脲（NMNU）的合成培养基中培养的大鼠气管外植体，检测其超微结构特征和粘蛋白基因表达的变化。在添加RA的培养物中，孵育48小时后，未检测到超微结构特征或粘蛋白基因表达的变化。然而，孵育96小时后，含有两种致癌物的培养物呈现出与鳞状表型相关的超微结构特征，且粘蛋白基因表达略有降低。因此，在视黄酸存在的情况下，致癌物诱导的细胞学向鳞状表型的变化与粘蛋白基因表达的显著丧失并不匹配。在不添加RA且添加或不添加致癌物的情况下培养48小时的外植体，未显示出与鳞状表型开始相关的任何细胞学变化。虽然仍能检测到粘蛋白mRNA，但与在添加RA的培养基中培养48小时的情况相比，其明显减少。然而，48小时后，所有外植体均表现出明显的鳞状化生，且粘蛋白信息降至痕量水平。因此，这些在添加RA和不添加RA的培养基中使用B[a]P和NMNU进行的实验结果表明，至少早期致癌物诱导的变化可能与控制粘液纤毛上皮粘蛋白成分表达的类视黄醇途径相关的变化不同。
