ABERRANT EXPRESSION OF NITRIC-OXIDE SYNTHASE IN HUMAN POLYPS, NEOPLASTIC COLONIC MUCOSA AND SURROUNDING PERITUMORAL NORMAL MUCOSA
ABERRANT EXPRESSION OF NITRIC-OXIDE SYNTHASE IN HUMAN POLYPS, NEOPLASTIC COLONIC MUCOSA AND SURROUNDING PERITUMORAL NORMAL MUCOSA
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DOI：
10.1093/carcin/15.10.2081
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发表时间：
1994-10-01
期刊：
影响因子：
4.7
通讯作者：
MOOCHHALA, SM
中科院分区：
文献类型：
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作者：
CHHATWAL, VJS;NGOI, SS;MOOCHHALA, SM
采用NAD(P)H diaphorase组织化学定位法研究一氧化氮合酶（NOS）在(i)作为对照的正常结肠粘膜单个细胞（n = 13）、（ii）结肠息肉（n = 14）、（iii）结肠癌（n = 20）和（iv）肿瘤周围（距离肿瘤2、5或10 cm）的表达。4例肿瘤标本癌旁有正常上皮，可作为内部控制。结肠癌组织中NOS活性表达较对照组显著降低（P < 0.004）；25%的人无法检测，45%的人减少，30%的人正常。正常黏膜与息肉组织中表达量比较，息肉组织中表达量明显降低（P < 0.027）；无法检测的占14%，减少的占35%，正常的占51%。与肿瘤周围2 cm和10 cm处相比，NOS活性表达显著降低（P < 0.001和P < 0.0001）。2、10 cm处表达量差异无统计学意义（P = 0.329）。离肿瘤2 cm处的瘤周粘膜与对照粘膜相比，差异无统计学意义（P = 1.000），但距离2 cm处的粘膜有NOS活性高表达的趋势。同样，在距离10 cm处获得的对照粘膜与瘤周粘膜之间无显著差异（P = 0.383）。用选择性NOS抑制剂L-NMMA预孵育后，所有组织中NOS活性的表达均被消除，而用D-NMMA未被消除。我们的数据显示，通过NAD(P)H diaphorase法发现NOS活性表达广泛且显著降低，从而反映了一氧化氮在结肠癌和结肠息肉中的活性。这种活性的普遍抑制，在明显的肿瘤发生之前，可能是结肠癌发生的一个重要事件。这种异常表达也可能与肿瘤促进和转移进展或肿瘤杀伤活性的选择性优势相一致。
The expression of nitric oxide synthase (NOS) was studied by NAD(P)H diaphorase histochemical localization method in (i) individual cells of the normal colonic mucosa (n = 13) which served as control, (ii) colonic polyps (n = 14), (iii) colonic carcinoma (n = 20) and (iv) peritumoral mucosa (2 and 5 or 10 cm away from the tumor). Four of the tumor specimens had normal epithelium adjacent to the cancer, which thus served as an internal control. The expression of NOS activity in colon cancer was significantly reduced as compared to the control group of individuals (P < 0.004); undetectable in 25%, diminished in 45%, normal in 30%. On comparing the expression in normal mucosa and polyps there was a significant reduction of the expression in polyps (P < 0.027); undetectable in 14%, reduced in 35%, normal in 51%. When compared to the peritumoral mucosa at 2 and 10 cm the tumor showed a significant reduction in expression of NOS activity (P < 0.001 and P < 0.0001 respectively). There was no significant difference seen in the expression at 2 and 10 cm (P = 0.329). The peritumoral mucosa at a distance of 2 cm away from the tumor when compared to the control mucosa showed no significant difference (P = 1.000), although there is a tendency to a high normal expression of NOS activity in the mucosa at a distance of 2 cm. Similarly, there was no significant difference between the control mucosa and the peritumoral mucosa obtained at a distance of 10 cm (P = 0.383). The expression of NOS activity in all tissues examined was abolished by preincubation of tissue with the selective NOS inhibitor L-NMMA but not with D-NMMA. Our data showed extensive and significant reduction as identified by the NAD(P)H diaphorase method in the expression of NOS activity, thereby reflecting the activity of nitric oxide in colon cancer and colonic polyps. The generalized suppression of this activity, which precedes the onset of overt neoplasia, may be an important event in colon carcinogenesis. This aberrant expression could also be compatible with the selective advantage to either tumor promotion and metastatic progression or to tumoricidal activity.