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巴西圣埃斯皮里图州肝细胞癌和肝硬化 TP53 突变分析反映了中水平的黄曲霉毒素膳食暴露。

Hepatocellular carcinoma and liver cirrhosis TP53 mutation analysis reflects a moderate dietary exposure to aflatoxins in Espírito Santo State, Brazil.

机构信息

Núcleo de Genética Humana e Molecular, Departamento de Ciências Biológicas, Centro de Ciências Humanas e Naturais, Universidade Federal do Espírito Santo, Av. Marechal Campos 1468, Campus de Maruípe, Vitória, Espírito Santo, CEP 29040-090, Brazil.

出版信息

Mol Biol Rep. 2013 Aug;40(8):4883-7. doi: 10.1007/s11033-013-2587-2. Epub 2013 May 7.

Abstract

The close relationship between aflatoxins and 249ser TP53 gene mutation (AGG to AGT, Arg to Ser) in hepatocellular carcinoma (HCC) makes this mutation an indirect indicator of dietary contamination with this toxin. We have examined the prevalence of codon 249 TP53 mutation in 41 HCC and 74 liver cirrhosis (without HCC) cases diagnosed at the HUCAM University Hospital in Vitoria, Espírito Santo State, Brazil. DNA was extracted from paraffin sections and from plasma. The mutation was detected by DNA amplification, followed by restriction endonuclease digestion and confirmed by direct sequencing. DNA restriction showed 249ser mutation in 16 HCC and 13 liver cirrhosis, but sequencing confirmed mutations in only 6 HCC and 1 liver cirrhosis. In addition, sequencing revealed 4 patients with mutations at codon 250 (250ser and 250leu) in HCC cases. The prevalence of TP53 mutation was 10/41 (24.3%) in HCC and 1/74 (1.4%) in liver cirrhosis. No relationship between the presence of mutations and the etiology of HCC was observed. TP53 exon 7 mutations, which are related to aflatoxins exposure, were found at 14.6% (249ser), 7.3% (250leu) and 2.4% (250ser) in 41 cases of HCC and 1.4% in 74 liver cirrhosis (without HCC) cases, suggesting a moderate dietary exposure to aflatoxins in the Espírito Santo State, Brazil.

摘要

黄曲霉毒素与肝癌中 249 位丝氨酸 TP53 基因突变(AGG 突变为 AGT,精氨酸变为丝氨酸)密切相关,使该突变成为这种毒素饮食污染的间接指标。我们检查了巴西圣埃斯皮里图州维多利亚市 HUCAM 大学医院诊断的 41 例肝癌和 74 例肝硬化(无肝癌)病例中 249 位 TP53 密码子突变的流行情况。从石蜡切片和血浆中提取 DNA。通过 DNA 扩增检测突变,然后用限制性内切酶消化,并通过直接测序确认。DNA 限制显示 16 例 HCC 和 13 例肝硬化存在 249 位丝氨酸突变,但测序仅证实 6 例 HCC 和 1 例肝硬化存在突变。此外,测序还发现 4 例 HCC 病例在 250 位密码子发生突变(250 位丝氨酸和 250 位亮氨酸)。肝癌中 TP53 突变的患病率为 10/41(24.3%),肝硬化中为 1/74(1.4%)。未观察到突变的存在与 HCC 的病因之间存在关系。在 41 例 HCC 病例中,TP53 外显子 7 突变与黄曲霉毒素暴露有关,分别为 14.6%(249 位丝氨酸)、7.3%(250 位亮氨酸)和 2.4%(250 位丝氨酸),而在 74 例无 HCC 的肝硬化病例中,这一比例为 1.4%,表明巴西圣埃斯皮里图州的饮食中存在中等程度的黄曲霉毒素暴露。

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