Enhancement of esophageal carcinogenesis in acid reflux model rats treated with ascorbic acid and sodium nitrite in combination with or without initiation
Enhancement of esophageal carcinogenesis in acid reflux model rats treated with ascorbic acid and sodium nitrite in combination with or without initiation
复制标题
抗坏血酸和亚硝酸钠联合或不联合治疗可增强胃酸反流模型大鼠的食管癌发生
作者：
Y. Kuroiwa;T. Okamura;Y. Ishii;T. Umemura;M. Tasaki;K. Kanki;K. Mitsumori;M. Hirose;A. Nishikawa
亚硝酸钠（NaNO2）和抗坏血酸（AsA）联合治疗已被证明可促进大鼠前胃癌的发生，可能是由于酸性条件下一氧化氮的产生。我们假设当胃酸反流降低腔内pH值时，类似的效果可能发生在食道。为了澄清这种可能性，研究人员给反流性食管炎模型大鼠（F344雄性）在饮用水中添加0.2% NaNO2，在饮食中添加1% AsA。在32周的联合治疗后，与基础饮食组相比，观察到食管中下部和最低部分上皮增生的发生率显著增加，并伴有不典型增生的加剧和病变的扩大。此外，仅在联合治疗组中发现1例鳞状细胞乳头状瘤。随后，我们证实了NaNO2和AsA共同处理对大鼠N -二（2 -羟丙基）亚硝胺引发的食管肿瘤发生模型的增强作用。所有节段增生的发生率都增加了，食管最低节段鳞状细胞乳头状瘤的发生率和多样性也增加了。因此，数据表明，NaNO2和AsA联合治疗对胃酸反流条件下大鼠食管癌的发生有促进作用，如在前胃。这些研究结果表明，过量摄入亚硝酸盐和抗氧化剂组合导致食管癌的风险是明显的，特别是在反流性食管炎患者中。（癌症科学2008；99:7-13）
Combined treatment with sodium nitrite (NaNO2) and ascorbic acid (AsA) has already been shown to promote rat forestomach carcinogenesis, possibly due to nitric oxide generation under acidic conditions. We hypothesized that a similar effect might occur in the esophagus when the luminal pH is decreased by acid reflux. To clarify this possibility, reflux esophagitis model rats (F344 male) were coadministered 0.2% NaNO2 in the drinking water and 1% AsA in the diet. After 32 weeks of the combined treatment, a significant increase in the incidence of epithelial hyperplasias of the lower‐middle and lowest parts of the esophagus were observed compared with the basal‐diet group, along with exacerbation of dysplasia and extension of the lesions. Additionally, one squamous cell papilloma was found only in the combined‐treatment group. Subsequently, we confirmed the enhancing effects of NaNO2 and AsA cotreatment in the rat N‐bis(2‐hydroxypropyl)nitrosamine‐initiated esophageal tumorigenesis model. The incidence of hyperplasia was enhanced in all segments, along with the incidence and multiplicity of squamous cell papillomas in the lowest segment of the esophagus. Thus, the data demonstrate that combined treatment with NaNO2 and AsA exerts promoting effects on rat esophageal carcinogenesis under acid reflux conditions, as in the forestomach. These findings suggest that the risk of excessive intake of a combination of nitrite and antioxidants for esophageal carcinogenesis is appreciable, particularly in patients with reflux esophagitis. (Cancer Sci 2008; 99: 7–13)
DOI：
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发表时间：
2006
期刊：
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影响因子：
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作者：
K. Wilson;Sidong;Fu;Kalathur;S. Ramanujam;Stephen;J. Meltzer
通讯作者：
K. Wilson;Sidong;Fu;Kalathur;S. Ramanujam;Stephen;J. Meltzer
影响因子：
3.9
作者：
A. Samouilov;P. Kuppusamy;Jay L. Zweier
通讯作者：
A. Samouilov;P. Kuppusamy;Jay L. Zweier