Rubio C A, Takayama S
Department of Pathology, Karolinska Institute, Stockholm, Sweden.
J Environ Pathol Toxicol Oncol. 1994;13(3):191-7.
We investigated the histologic phenotype of experimentally induced colonic tumors in 412 rats: 300 Sprague-Dawley rats (treated with dimethylhydrazine = DMH) and 112 F-344 rats (treated with glutamic acid pyrolysate = Glu). Of the 300 DMH-treated Sprague-Dawley rats, 278 (92.6%) developed a total of 358 colonic tumors: 60 adenomas and 298 invasive adenocarcinomas. Of the 60 adenomas, 45 (75.0%) were exophytic adenomas and the remaining 15 (25.0%) were flat adenomas. Of the 298 adenocarcinomas, 82 (27.5%) were exophytic adenocarcinomas arising in exophytic adenomas, 39 (13%) were flat adenocarcinomas originating in flat adenomas (n = 38) or intramucosal (n = 1), 90 (30.2%) were lymphoid-associated adenocarcinomas (LAC), arising in lymphoid-associated mucosa, and the remaining 87 (29.2%) were overt adenocarcinomas (usually signet-ring cell type carcinomas). In contrast, among the 112 Glu-treated F-144 rats, 62 (55.3%) developed a total of 63 colonic tumors: 52 adenomas and 11 adenocarcinomas. All 52 adenomas were exophytic adenomas and all 11 adenocarcinomas were exophytic tumors originating in exophytic adenomas. No flat neoplastic lesions or LAC were found. Glu-tumors were located predominantly in the cecum and in the right colon and were either tubular adenomas or tubular adenocarcinomas. In contrast, the tumors in the cecum and in the right colon in DMH-treated rats were usually LAC of signet-ring cell type. Neither flat adenomatous lesions (flat adenomas or flat adenocarcinomas) nor LAC were recorded in F-344 rats treated with Glu. The colonic adenomas found in the F-344 rats attained a huge size (when compared with those seen in DMH-treated rats). While the cause(s) of the difference in the histologic phenotypes and their localization as well as of the difference in the size of the tumors between the two experimental groups remains unclear, it is conceivable that Glu binds, mutates, suppresses, or interacts with oncogenes in colonic epithelial cells in a different fashion than DMH. A review of the literature indicates that the genetic differences in the two strains of rats used in the present work may not account for the difference in the results obtained.
我们研究了412只大鼠实验性诱导结肠肿瘤的组织学表型：300只斯普拉格-道利大鼠（用二甲基肼 = DMH处理）和112只F-344大鼠（用谷氨酸热解产物 = Glu处理）。在300只经DMH处理的斯普拉格-道利大鼠中，278只（92.6%）共发生358个结肠肿瘤：60个腺瘤和298个浸润性腺癌。在60个腺瘤中，45个（75.0%）为外生性腺瘤，其余15个（25.0%）为扁平腺瘤。在298个腺癌中，82个（27.5%）为起源于外生性腺瘤的外生性腺癌，39个（13%）为起源于扁平腺瘤（n = 38）或黏膜内（n = 1）的扁平腺癌，90个（30.2%）为淋巴样相关腺癌（LAC），起源于淋巴样相关黏膜，其余87个（29.2%）为明显腺癌（通常为印戒细胞型癌）。相比之下，在112只经Glu处理的F-144大鼠中，62只（55.3%）共发生63个结肠肿瘤：52个腺瘤和11个腺癌。所有52个腺瘤均为外生性腺瘤，所有11个腺癌均为起源于外生性腺瘤的外生性肿瘤。未发现扁平肿瘤性病变或LAC。Glu诱导的肿瘤主要位于盲肠和右结肠，为管状腺瘤或管状腺癌。相比之下，DMH处理大鼠的盲肠和右结肠肿瘤通常为印戒细胞型LAC。在用Glu处理的F-344大鼠中未记录到扁平腺瘤性病变（扁平腺瘤或扁平腺癌）或LAC。F-344大鼠中发现的结肠腺瘤体积巨大（与DMH处理大鼠中的腺瘤相比）。虽然两个实验组之间组织学表型及其定位差异以及肿瘤大小差异的原因尚不清楚，但可以想象Glu与结肠上皮细胞中的癌基因结合、突变、抑制或相互作用的方式与DMH不同。文献综述表明，本研究中使用的两种大鼠品系的遗传差异可能无法解释所获得结果的差异。
