Lam L K, Garg P
Gray Freshwater Biological Institute, University of Minnesota, Navarre 55392.
Carcinogenesis. 1991 Jul;12(7):1341-4. doi: 10.1093/carcin/12.7.1341.
The di-tert-butyl-substituted hydroxyanisoles 2,5-di-tert-butyl-4-hydroxyanisole (2,5-DTBHA) and 3,5-di-tert-butyl-4-hydroxyanisole (3,5-DTBHA) are contaminants of the commercial antioxidant butylated hydroxyanisole. The tumorigenicity of 2,5-DTBHA, 3,5-DTBHA, 2,5-di-tert-butyl hydroquinone (2,5-DTBHQ), a demethylated analog of 2,5-DTBHA, and 3-tert-butyl-4-hydroxyanisole (3-BHA) were investigated. Dietary 3-BHA, which has been shown previously to induce neoplastic lesions in the hamster forestomach, was found to cause the development of forestomach papilloma in 75% of the hamsters in 24 weeks at 1% addition to the diet. General thickening of the forestomach lining with moderate to severe hyperkeratosis and hyperplasia were observed in 14 (88%) of the 16 hamsters in this group. Inflammation was generally found in the forestomach of these animals. Similar observations were found in 14 (88%) of the 16 hamsters in the group that was fed 1% DTBHQ. Severe hyperplasia and papilloma found in the forestomach of these hamsters were similar in severity to those in the 3-BHA group. Unlike the 3-BHA and 2,5-DTBHQ groups, the forestomachs of 1% 2,5-DTBHA and 3,5-DTBHA treated animals were not different from the hamsters in the control group. Only mild hyperplasia at or near the limiting ridge was found in the forestomach of some of these animals. Hyperkeratosis or inflammation were not observed. Steric factors may play a role in the lack of tumorigenicity of 2,5-DTBHA and 3,5-DTBHA, while the formation of a stable free radical from 2,5-DTBHQ may be the activated species responsible for its tumorigenicity.
二叔丁基取代的羟基茴香醚2,5 - 二叔丁基 - 4 - 羟基茴香醚（2,5 - DTBHA）和3,5 - 二叔丁基 - 4 - 羟基茴香醚（3,5 - DTBHA）是商业抗氧化剂丁基羟基茴香醚的污染物。研究了2,5 - DTBHA、3,5 - DTBHA、2,5 - 二叔丁基对苯二酚（2,5 - DTBHQ，2,5 - DTBHA的去甲基类似物）和3 - 叔丁基 - 4 - 羟基茴香醚（3 - BHA）的致瘤性。先前已证明膳食中的3 - BHA可诱导仓鼠前胃发生肿瘤性病变，在饲料中添加1%的3 - BHA，24周后发现75%的仓鼠发生了前胃乳头瘤。在该组16只仓鼠中的14只（88%）观察到前胃黏膜普遍增厚，伴有中度至重度角化过度和增生。这些动物的前胃中普遍发现有炎症。在喂食1% DTBHQ的组中，16只仓鼠中的14只（88%）也有类似观察结果。这些仓鼠前胃中发现的严重增生和乳头瘤的严重程度与3 - BHA组相似。与3 - BHA和2,5 - DTBHQ组不同，用1% 2,5 - DTBHA和3,5 - DTBHA处理的动物的前胃与对照组仓鼠没有差异。在这些动物中的一些前胃中仅在界限嵴处或其附近发现轻度增生。未观察到角化过度或炎症。空间因素可能在2,5 - DTBHA和3,5 - DTBHA缺乏致瘤性中起作用，而2,5 - DTBHQ形成稳定自由基可能是其致瘤性的活性物质。
