Abstract

This study investigated whether valproic acid (VPA, a histone deacetylase inhibitor) can interfere with the carcinogenicity of polycyclic aromatic hydrocarbons (PAHs). A typical representative compound of PAHs, 7,12-Dimethylbenz[a]anthracene (DMBA), was used to induce rat breast cancer. The results showed that therapeutic concentration of VPA (50 and 100 mg/kg) delayed the occurrence of tumors, reduced tumor formation rate and attenuated tumors growth, and have a protective effect on normal tissues. The macrophage-mediated inflammatory response was found to be associated with the observed effect of VPA. In addition, we screened and validated a possible gene, Sema3c, which was involved in DMBA-induced breast cancer development and can be inhibited by VPA.

中文翻译：

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丙戊酸对环境致癌物多环芳烃致肿瘤的干预作用

摘要

本研究调查了丙戊酸（VPA，一种组蛋白去乙酰化酶抑制剂）是否会干扰多环芳烃 (PAH) 的致癌性。PAHs的典型代表化合物7,12-二甲基苯并[a]蒽(DMBA)用于诱导大鼠乳腺癌。结果表明，治疗浓度的VPA（50和100 mg/kg）延缓了肿瘤的发生，降低了肿瘤形成率，减缓了肿瘤的生长，对正常组织有保护作用。发现巨噬细胞介导的炎症反应与观察到的 VPA 作用有关。此外，我们筛选并验证了一个可能的基因Sema3c，该基因参与 DMBA 诱导的乳腺癌发展，并且可以被 VPA 抑制。