Chemoprevention of mouse colon tumors with difluoromethylornithine during and after carcinogen treatment.
Chemoprevention of mouse colon tumors with difluoromethylornithine during and after carcinogen treatment.
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在致癌剂治疗期间和之后用二氟甲基鸟氨酸对小鼠结肠肿瘤进行化学预防。
作者：
M. Tempero;K. Nishioka;K. Knott;R. K. Zetterman
α-二氟甲基鸟氨酸（DFMO）治疗已显示在许多实验肿瘤模型（包括皮肤、乳腺和结肠）中改变致癌作用。本研究旨在确定DFMO治疗是否可以抑制致癌物治疗后的实验小鼠结肠肿瘤，以及DFMO对结肠粘膜细胞增殖的相关作用是否发生。雄性CD 1小鼠（每组40只）接受二甲肼（30 mg/kg/周x 6周，s.c.）和各种DFMO时间表，1%饮用水：A组，无; B组，二甲肼处理后; C组，二甲肼处理期间; D组，在整个研究中持续。红细胞多胺水平的测量结果表明，DFMO治疗消融腐胺水平，并证实，实现了全身生物学效应。肿瘤数据分析显示DFMO治疗对结肠肿瘤具有显著的抑制作用与对照组A相比，B组（24%）和D组（20%）的（腺瘤和腺癌）发生率（52%，P <0.05 A vs B，P <0.02 A vs D）和肛门鳞状细胞癌（A与B的P小于0.001，A与C的P小于0.05，A与D的P小于0.05）。DFMO处理对结肠粘膜中的细胞增殖没有一致的影响。本研究支持DFMO治疗改变小鼠结肠肿瘤发生后起始阶段事件的假设。
alpha-Difluoromethylornithine (DFMO) treatment has been shown to modify carcinogenesis in many experimental tumor models, including skin, breast, and colon. This study was designed to determine whether DFMO treatment can inhibit experimental mouse colon tumors after carcinogen treatment and whether an associated effect of DFMO on cell proliferation in colon mucosa occurs. Male CD1 mice (40 per group) received dimethylhydrazine (30 mg/kg/week x 6 weeks, s.c.) and various schedules of DFMO, 1% in drinking water: Group A, none; Group B, following dimethylhydrazine treatment; Group C, during dimethylhydrazine treatment; and Group D, continuously throughout the study. Measurements of RBC polyamine levels showed that DFMO treatment ablated putrescine levels and confirmed that a systemic biological effect was achieved. Analysis of tumor data showed a significant inhibitory effect of DFMO treatment on colon tumor (adenomas and adenocarcinomas) incidence in Groups B (24%) and D (20%) compared to control Group A (52%, P less than 0.05 A versus B, P less than 0.02 A versus D) and on squamous cell carcinomas of the anus in all groups (P less than 0.001 A versus B, P less than 0.05 A versus C, A versus D). No consistent effect of DFMO treatment on cell proliferation in colon mucosa was identified. This study supports the hypothesis that DFMO treatment alters events in the postinitiation phases of mouse colon tumorigenesis.