Inhibitory effects of β-carotene and vitamin A during the progression phase of hepatocarcinogenesis involve inhibition of cell proliferation but not alterations in DNA methylation
Inhibitory effects of β-carotene and vitamin A during the progression phase of hepatocarcinogenesis involve inhibition of cell proliferation but not alterations in DNA methylation
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DOI：
10.1207/s15327914nc441_11
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发表时间：
2002-01-01
影响因子：
2.9
通讯作者：
Ong, TP
中科院分区：
文献类型：
--
作者：
Moreno, FS;S-Wu, T;Ong, TP
研究了在肝癌发生的抗性肝细胞模型的进展阶段给予大鼠β-胡萝卜素和维生素A的抑制作用。β-胡萝卜素和维生素A处理的动物倾向于出现肝癌，在处死时肝癌的发生率低于对照组。维生素A，而不是β-胡萝卜素，管理也往往减少持续肝细胞结节的总数。苏木精和伊红染色切片的组织学检查证实了这些结果。这表明两种化合物在持续性结节向癌症的转化过程中表现出抑制作用，而只有类维生素A也能够抑制持续性结节的演变或使其消退。此外，β-胡萝卜素和维生素A治疗的动物表现出较低的肝溴脱氧尿苷标记指数在肿瘤病变以及在邻近的正常组织比对照组，这表明这些物质对细胞增殖的抑制作用。然而，β-胡萝卜素和维生素A的施用均未导致羟甲基戊二酰辅酶A还原酶、c-myc和c-Ha-ras基因的CCGG序列甲基化模式的实质性改变，其产物与细胞增殖和致癌相关。因此，β-胡萝卜素和维生素A对肝癌进展的抑制作用似乎与DNA甲基化无关。
The inhibitory effects of beta-carotene and vitamin A administered to rats in the progression phase of the resistant hepatocyte model of hepatocarcinogenesis were investigated. beta-Carotene- and vitamin A-treated animals tended to present, with a lower incidence of hepatic cancers than controls at sacrifice. Vitamin A, but not beta-carotene, administration also tended to reduce the total number of persistent hepatocyte nodules. Histological examination of sections stained with hematoxylin and eosin confirmed these results. This suggests that both compounds exhibit inhibitory effects during conversion of persistent nodules to cancers, whereas only the retinoid is also capable of inhibiting the evolution of persistent nodules or causing them to regress. Moreover, beta-carotene- and vitamin A-treated animals showed lower hepatic bromodeoxyuridine labeling indexes in neoplastic lesions as well as in adjacent normal tissues than controls, suggesting an inhibitory action of these substances on cell proliferation. However, neither beta-carotene nor vitamin A administration resulted in substantial alterations in the CCGG sequence methylation pattern of hydroxymethylglutaryl coenzyme A reductase, c-myc, and c-Ha-ras genes, the products of which are related to cell proliferation and carcinogenesis. Therefore, these inhibitory effects of beta-carotene and vitamin A on progression of hepatocarcinogenesis do not seem to be related to DNA methylation.