Ghanayem B I, Matthews H B, Maronpot R R
National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Toxicol Pathol. 1991;19(3):273-9. doi: 10.1177/019262339101900310.
In a chronic study conducted by the National Toxicology Program (NTP), gavage administration of 100 or 200 mg ethyl acrylate (EA)/kg/day, 5 days/week, to F344 rats and B6C3F1 mice resulted in a significant dose-dependent increase in the incidence of squamous cell papillomas and carcinomas of the forestomach of both sexes of rats and mice. No increase in the incidence of tumors was observed at any other site in these rats. Chemically-induced cell proliferation is currently thought to play a role in the development and progression of chemically-induced neoplasia. Therefore, a stop-study was initiated where 100 or 200 mg EA/kg (in corn oil) was administered daily, 5 days/week, for 13 weeks. Rats sacrificed at the end of the treatment regimen had severe epithelial hyperplasia of the forestomach. No lesions were observed in the glandular stomach or liver of EA-treated rats. Forestomach hyperplasia induced by EA included upward and downward cell proliferation. However, forestomachs of rats treated for 13 weeks and sacrificed 8 weeks after the last EA dose exhibited a significant decline in the incidence and severity of forestomach mucosal hyperplasia. Histopathologic evaluation of forestomachs of EA-treated rats (13 weeks) which were allowed a 19-month-recovery (with no exposure to EA) showed further decline in the incidence and severity of mucosal cell hyperplasia. These results indicate that gavage administration of EA to rats results in extensive and sustained forestomach mucosal hyperplasia. The sustainability of forestomach hyperplasia is apparently dependent on the continued exposure of rats to ethyl acrylate, and regressed after cessation of dosing. Furthermore, although enough post-treatment time was allowed for tumors to develop after cessation of EA administration, forestomachs exhibited a nearly complete recovery with no increased incidence of papillomas or carcinomas. It, therefore, remains to be determined what duration of exposure or other factors are critical for reversibility or progression of EA-induced forestomach mucosal hyperplasia to neoplasia.
在国家毒理学计划（NTP）进行的一项长期研究中，每周5天，以100或200毫克丙烯酸乙酯（EA）/千克/天的剂量对F344大鼠和B6C3F1小鼠进行灌胃给药，导致大鼠和小鼠两性前胃鳞状细胞乳头瘤和癌的发生率出现显著的剂量依赖性增加。在这些大鼠的任何其他部位均未观察到肿瘤发生率增加。目前认为化学诱导的细胞增殖在化学诱导的肿瘤形成和发展中起作用。因此，启动了一项停药研究，每天（每周5天）给予100或200毫克EA/千克（溶于玉米油），持续13周。在治疗方案结束时处死的大鼠前胃有严重的上皮增生。在接受EA治疗的大鼠的腺胃或肝脏中未观察到病变。EA诱导的前胃增生包括向上和向下的细胞增殖。然而，接受13周治疗并在最后一次EA剂量后8周处死的大鼠前胃，其前胃黏膜增生的发生率和严重程度显著下降。对接受EA治疗13周的大鼠前胃进行组织病理学评估，在允许19个月恢复（不接触EA）后，黏膜细胞增生的发生率和严重程度进一步下降。这些结果表明，对大鼠灌胃EA会导致广泛且持续的前胃黏膜增生。前胃增生的持续性显然取决于大鼠持续接触丙烯酸乙酯，给药停止后会消退。此外，尽管在停止EA给药后给予了足够的治疗后时间让肿瘤发展，但前胃几乎完全恢复，乳头瘤或癌的发生率没有增加。因此，仍有待确定何种暴露持续时间或其他因素对于EA诱导的前胃黏膜增生向肿瘤的可逆性或进展至关重要。
