Biochemical, pathologic and morphometric alterations induced in male B6C3F1 mouse liver by short-term exposure to dichloroacetic acid
Biochemical, pathologic and morphometric alterations induced in male B6C3F1 mouse liver by short-term exposure to dichloroacetic acid
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DOI：
10.1016/0378-4274(95)03409-9
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发表时间：
1995-11-01
影响因子：
3.5
通讯作者：
DeAngelo, AB
中科院分区：
文献类型：
--
作者：
Carter, JH;Carter, HW;DeAngelo, AB
二氯乙酸（DCA）在雄性B6C3F1小鼠中是一种完全的肝癌原和肿瘤启动子。已发表的报告表明，该化合物没有基因毒性。本研究探讨了可能的非遗传毒性（表观遗传）机制，DCA引起其致癌反应。利用相关的生化、病理和形态计量学技术来表征和定量雄性B6C3F1小鼠肝细胞对含DCA饮用水的急性、短期反应。细胞结构、[H-3]胸苷结合、DNA浓度、核大小和双核是根据暴露水平（0、0.5和5 g/l）和暴露于DCA的时间长短来评估的。暴露于DCA 30天或更短时间的动物肝细胞的剂量相关变化表明，短期暴露于DCA会抑制有丝分裂、改变细胞代谢和改变倍性类别。因此，DCA致癌作用可能涉及细胞适应性、耐药性的发展和具有生长优势的表型改变细胞的选择。
Dichloroacetic acid (DCA) is a complete hepatocarcinogen and tumor promoter in the male B6C3F1 mouse. Published reports indicate that the compound is non-genotoxic. This study examines possible non-genotoxic (epigenetic) mechanisms by which DCA elicits its carcinogenic response. Correlative biochemical, pathologic and morphometric techniques are used to characterize and quantify the acute, short-term response of hepatocytes in the male B6C3F1 mouse to drinking water containing DCA. Cellularity, [H-3]thymidine incorporation, DNA concentration, nuclear size, and binuclearity are evaluated in terms of level of exposure (0, 0.5 and 5 g/l) and length of exposure to DCA, The dose-related alterations in hepatocytes of animals exposed to DCA for 30 days or less indicate that shortterm exposure to DCA results in inhibition of mitoses, alterations in cellular metabolism and a shift in ploidy class. Thus, DCA carcinogenesis may involve cellular adaptations, development of drug resistance and selection of phenotypically altered cells with a growth advantage.