Chemoprevention of MNU-induced mammary tumors in the mature rat by 4-HPR and tamoxifen.
Chemoprevention of MNU-induced mammary tumors in the mature rat by 4-HPR and tamoxifen.
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发表时间：
1992-07
影响因子：
2
通讯作者：
R. Moon;Kelloff Gj;D. Cj;V. Steele;Thomas Cf;C. Sigman
中科院分区：
文献类型：
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作者：
R. Moon;Kelloff Gj;D. Cj;V. Steele;Thomas Cf;C. Sigman
在120日龄雌性Sprague-Dawley大鼠中评价了类维生素A全反式-N-（4-羟基苯基）-维A酰胺（4-HPR）和抗雌激素枸橼酸他莫昔芬（tamoxifen citrate）对N-甲基-N'-亚硝基脲（MNU）诱导的乳腺癌的化学预防效力。单独和组合测试试剂。从50 mg MNU/kg-bw单次静脉给药前60天开始，以改良AIN-76A饲料给药，并持续至研究结束，即致癌物处理后180天。在782毫克/公斤的饮食，4-HPR单独显着抑制乳腺癌的诱导相比，致癌物控制。在0.250毫克/公斤的饮食，他莫昔芬单独降低肿瘤的发病率相比，致癌物控制。在0.125 mg/kg饲料时，他莫昔芬无效。782 mg 4-HPR/kg饲料与0.250或0.125 mg他莫昔芬/kg饲料的组合有效抑制MNU诱导的腺癌。这些组合的肿瘤发生率的降低大于单独使用任何一种药物。4-与致癌物对照组相比，HPR和0.250 mg他莫昔芬/kg饮食使肿瘤发生率降低81%（p <0.005），而4-HPR和0.125 mg他莫昔芬/kg饮食使肿瘤发生率降低72%（p <0.005）。还测试了391 mg 4-HPR/kg饮食和0.500 mg他莫昔芬/kg饮食的组合，并且其在降低肿瘤发病率方面是有效的。
The chemopreventive efficacies of the retinoid all-trans-N-(4-hydroxyphenyl)-retinamide (4-HPR) and the anti-estrogen tamoxifen citrate were evaluated against N-methyl-N'-nitrosourea (MNU) induced mammary cancer in 120-day old female Sprague-Dawley rats. The agents were tested alone and in combination. They were administered in a modified AIN-76A diet, beginning 60 days prior to a single i.v. dose of 50 mg MNU/kg-bw and continuing until the end of the study, 180 days post-carcinogen treatment. At 782 mg/kg diet, 4-HPR alone significantly inhibited the induction of mammary adenocarcinomas compared with carcinogen controls. At 0.250 mg/kg diet, tamoxifen alone reduced tumor incidence compared with carcinogen controls. At 0.125 mg/kg diet, tamoxifen was ineffective. Combinations of 782 mg 4-HPR/kg diet with either 0.250 or 0.125 mg tamoxifen/kg diet were effective in inhibiting MNU-induced adenocarcinomas. The reductions in tumor incidence were greater for these combinations than for either agent alone. 4-HPR and 0.250 mg tamoxifen/kg diet decreased tumor incidence 81% (p less than 0.005), whereas 4-HPR and 0.125 mg tamoxifen/kg diet decreased tumor incidence 72% (p less than 0.005) compared with carcinogen controls. The combination of 391 mg 4-HPR/kg diet and 0.500 mg tamoxifen/kg diet was also tested and was effective in reducing tumor incidence.