用苯并[a]芘和 SARS-COV-2 疫苗抗原修饰的 TR53 共抑制基因在体外实验中的表达

O. Dolgikh, O. A. Kazakova
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引用次数: 0

摘要

导言。化学和生物环境因素的影响与心血管疾病和癌症相关疾病的遗传易感性风险有关,这就决定了寻找 mRNA 结构早期紊乱的遗传指标标记的相关性。 材料和方法。对健康志愿者全血细胞培养中的 TP53 rs1042522 基因多态性以及 TP53 hs1034249_m1 转录本的相对归一化表达水平进行了分析,包括自发表达和经苯并[a]芘和 SARS-CoV-2 疫苗抗原(浓度为 0.006 mg/kg)24 小时孵育诱导表达。毫升)进行了实验。 结果对自发和抗原诱导的 TP53 hs1034249_m1 mRNA 表达水平进行比较分析,确定了与 TP53 rs1042522 基因多态性特征相关的个体和群体相对表达值。在 CG rs1042522 基因型的情况下,苯并[a]芘和 SARS-CoV-2 对 hs1034249_m1 TP53 基因的表达有相反的影响,而苯并[a]芘和 SARS-CoV-2 的联合影响(反映了对 hs00900055_m1 TP53 基因表达的抑制)与 GG 基因型有关。 该研究的局限性在于使用的样本相对较少,且全血样本数量有限。 结论6 µg/L 浓度的苯并[a]芘和 SARS-CoV-2 能够改变体外 TP53 细胞凋亡基因的表达、因此,可以认为苯并[a]芘诱导的 TP53 基因 hs00900055_m1 的表达增加是病毒感染(SARS-CoV-2)恶化的机制之一,这与 CG TP53 rs1042522 杂合子变体的所有者失去控制炎症发展(其增殖阶段)的 p53 有关。在变异单卵多态 GG TP53 rs1042522 的情况下,苯并[a]芘和 SARS-CoV-2 的结合会导致 TP53 基因 hs00900055_m1 mRNA 的表达受到抑制,表现为气喘、免疫抑制和免疫增殖并发症的形成。建议将 TP53 基因 hs00900055_m1 转录本作为诊断与 SARS-CoV-2+ 苯并[a]芘联合感染相关的早期疾病的指标。该实验模拟了影响因素真实组合的自然条件。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Expression of the TR53 oncosuppressor gene modified with benzo[a]pyrene and the SARS-COV-2 vaccine antigen in an in vitro experiment
Introduction. The impact of chemical and biological environmental factors is associated with the risk of a genetic predisposition to the development of cardiovascular and cancer-associated diseases, which determines the relevance of the search for genetic indicator markers of early disorders in the mRNA structure. Materials and methods. The analysis of TP53 rs1042522 gene polymorphism, as well as the relative normalized expression level of TP53 hs1034249_m1 transcript, in whole blood cell culture in healthy volunteers, both spontaneous and induced by 24-hour incubation with benzo[a]pyrene and SARS-CoV-2 vaccine antigen (at concentrations of 0.006 mg/kg). Ml), was conducted. Results. Comparative analysis of spontaneous and antigen-induced levels of TP53 hs1034249_m1 mRNA expression allowed establishing individual and group values of relative expression associated with the polymorphism features of the TP53 rs1042522 gene. Benzo[a]pyrene and SARS-CoV-2 were found to have opposite effects on the expression of hs1034249_m1 TP53 genes in the case of the CG rs1042522 genotype, while the combined effect of benzo[a]pyrene and SARS-CoV-2, which reflected the inhibition of the expression of hs00900055_m1 of the TP53 gene was associated with the GG genotype. The limitations of the study are the use of a relatively small sample and a limited number of whole blood samples. Conclusion. The ability of benzo[a]pyrene and SARS-CoV-2 at concentrations of 6 µg/L to modify the expression of the TP53 apoptosis gene in vitro has been shown, which makes it possible to consider the increase in the expression of hs00900055_m1 of the TP53 gene induced by benzo[a]pyrene as one of the mechanisms for aggravating the course of viral infections (SARS-CoV-2) in connection with loss of p53-controlling for the development of inflammation (its proliferative phase) for owners of the heterozygous variant of CG TP53 rs1042522. In the case of variant monozygotic polymorphism GG TP53 rs1042522, the combination of benzo[a]pyrene and SARS-CoV-2 leads to inhibition of the expression of hs00900055_m1 mRNA of the TP53 gene, which is phenotypically reflected by the formation of asthenia, immunosuppression and onco-proliferative complications. The hs00900055_m1 transcript of the TP53 gene is recommended as an indicator for the tasks of diagnosing early disorders associated with the combination of SARS-CoV-2+ benzo[a]pyrene. The experiment simulates the natural conditions of real combinations of influencing factors.
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