Comparative activity of N-(4-hydroxyphenyl)-all-trans-retinamide and alpha-difluoromethylornithine as inhibitors of lymphoma induction in PIM transgenic mice.
Comparative activity of N-(4-hydroxyphenyl)-all-trans-retinamide and alpha-difluoromethylornithine as inhibitors of lymphoma induction in PIM transgenic mice.
复制标题
N-(4-羟基苯基)-全反式-视黄酰胺和α-二氟甲基鸟氨酸作为 PIM 转基因小鼠淋巴瘤诱导抑制剂的活性比较。
DOI：
10.1093/carcin/17.11.2513
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发表时间：
1996
期刊：
影响因子：
4.7
通讯作者：
Kelloff,GJ
中科院分区：
文献类型：
--
作者：
McCormick,DL;Johnson,WD;Rao,KV;Bowman-Gram,T;Steele,VE;Lubet,RA;Kelloff,GJ
评估了类视黄醇 N-(4-羟苯基)-全反式视黄酰胺 (4-HPR) 和多胺合成抑制剂 α-二氟甲基鸟氨酸 (DFMO) 作为 PIM 转基因小鼠淋巴瘤诱导抑制剂的活性。通过单次腹膜内注射每公斤体重 50 毫克 N-乙基-N-亚硝基脲 (ENU) 来诱导雄性 PIM 小鼠发生淋巴瘤。 ENU 给药后立即开始连续饮食给予 4-HPR（391、196 或 98 mg/kg 饮食）或 DFMO（1000、500 或 250 mg/kg 饮食），并持续到第 35 周研究结束。 ENU 后 20 周，高剂量的 4-HPR 降低了淋巴瘤发病率和相关死亡率。然而，4-HPR 提供的保护作用代表了肿瘤发展的延迟而不是抑制，因为研究终止时的淋巴瘤发病率和死亡率在饮食对照组和所有用 4-HPR 治疗的组中相似。在研究的任何阶段，DFMO 对淋巴瘤的发病率、潜伏期或死亡率都没有影响。这些结果表明4-HPR或其他类视黄醇可能有效预防淋巴瘤诱导，而抑制多胺生物合成似乎并未为淋巴肿瘤的化学预防提供有用的机制目标。 PIM转基因小鼠为快速评估化学预防剂提供了有用的体内模型。
The activities of the retinoid,N-(4-hydroxyphenyl)-all-trans-retinamide (4-HPR) and the polyamine synthesis inhibitor, α-difluoromethylornithine (DFMO), as inhibitors of lymphoma induction in PIM transgenic mice were evaluated. Lymphoma was induced in male PIM mice by a single intraperitoneal injection of 50 mgN-ethyl-N-nitrosourea (ENU) per kg body weight. Continuous dietary administration of 4-HPR (391, 196 or 98 mg/kg diet) or DFMO (1000, 500 or 250 mg/kg diet) was initiated immediately after ENU administration, and was continued until the end of the study at 35 weeks. At 20 weeks post-ENU, the high dose of 4-HPR reduced both lymphoma incidence and associated mortality. However, the protection conferred by 4-HPR represented a delay rather than an inhibition of neoplastic development, since both lymphoma incidence and mortality at study termination were similar in dietary controls and all groups treated with 4-HPR. DFMO had no effect on lymphoma incidence, latency or mortality at any point in the study. These results suggest that 4-HPR or other retinoids may be effective in the prevention of lymphoma induction, whereas inhibition of polyamine biosynthesis does not appear to present a useful mechanistic target for the chemoprevention of lymphoid neoplasia. The PIM transgenic mouse provides a usefulin vivomodel for the rapid evaluation of chemopreventive agents.