Chandra Sundeep A, Nolan Michael W, Malarkey David E
Safety Assessment, GlaxoSmithKline, Research Triangle Park, NC 27709, USA. sundeep.a.chandra.gsk.com
Toxicol Pathol. 2010 Jan;38(1):188-97. doi: 10.1177/0192623309356452. Epub 2009 Dec 17.
Cancers of the stomach and large intestine (LI) are the second and fourth leading causes of human cancer mortality. A review of the National Toxicology Program (NTP) database and the Carcinogenic Potency Database (CPDB) reveals that chemically induced neoplasms of the gastrointestinal tract (GIT) are relatively common. Within the GIT, epithelial tumors of the forestomach in mice and rats and LI of the rat are most common. Generally, there is a high species concordance for forestomach with at least 26 chemicals inducing tumors in both species. Glandular stomach tumors are rare, and the few reported are usually neuroendocrine tumors (carcinoids) originating from the enterochromaffin-like (ECL) cells. Of 290 carcinogenic agents identified by the NTP, 19 (7%) caused intestinal neoplasia, 14 in the rat and 5 in the mouse. Neoplasms occurred in both males and females, exclusively in the small intestine (SI) of the mouse and in the LI or both SI and LI in the rat. Enteric carcinogens (NTP) frequently induced neoplasms at other alimentary sites (oral cavity, esophagus, and stomach). In conclusion, the most common induced GIT tumors are squamous neoplasms of the forestomach, glandular neoplasms of the stomach are rare, and rats appear more prone to developing LI (colorectal) cancer compared to mice.
胃癌和大肠癌是导致人类癌症死亡的第二和第四大主要原因。对国家毒理学计划（NTP）数据库和致癌潜能数据库（CPDB）的回顾显示，化学诱导的胃肠道（GIT）肿瘤相对常见。在胃肠道内，小鼠和大鼠前胃的上皮肿瘤以及大鼠的大肠癌最为常见。一般来说，前胃肿瘤在物种间具有较高的一致性，至少有26种化学物质可在两种物种中诱发肿瘤。腺胃肿瘤很少见，少数报告的通常是起源于肠嗜铬样（ECL）细胞的神经内分泌肿瘤（类癌）。在NTP确定的290种致癌物质中，19种（7%）导致肠道肿瘤，其中14种在大鼠中诱发，5种在小鼠中诱发。肿瘤在雄性和雌性中均有发生，小鼠仅发生在小肠（SI），大鼠则发生在大肠或同时发生在小肠和大肠。肠道致癌物（NTP）经常在其他消化道部位（口腔、食管和胃）诱发肿瘤。总之，最常见的诱导性胃肠道肿瘤是前胃的鳞状肿瘤，胃的腺性肿瘤很少见，与小鼠相比，大鼠似乎更容易发生大肠癌。
