4-硝基喹啉 N-氧化物 (4-NQO) 及其衍生物与基因组 DNA 反应形成稳定的喹诺酮单加合物，具有高度诱变性和遗传毒性。虽然上皮细胞长期高剂量暴露于 4-NQO 等致癌物质会导致肿瘤发展，但其对其他细胞的影响尚未被探索。由于异常免疫学特征导致的免疫抑制被认为是肿瘤的一个重要原因，因此我们在体内和体外确定了 4-NQO 与免疫细胞之间的相互作用，及其对口腔鳞状细胞癌 (OSCC) 进展的影响。小鼠模型。脾脏和外周血的免疫细胞分析显示，与未治疗组相比，4-NQO 暴露小鼠的 B 细胞群显着减少。此外，γδ T 和 CD5 B 淋巴细胞群在 OSCC 癌前和癌后阶段均减​​少。这些结果表明，4-NQO 通过全身改变某些免疫细胞，诱导肿瘤从癌前病变转变为 OSCC。接下来，为了确定 4-NQO 对免疫细胞的影响，对人类 B 细胞系和 T 细胞系进行了 4-NQO 处理； B 细胞中细胞活力的降低、DNA 损伤反应标记物的增加以及细胞凋亡的诱导比 T 细胞更明显。总而言之，我们的结果表明，除了口腔上皮细胞的遗传毒性外，4-NQO还增强了对特定免疫细胞的长期影响，诱导细胞死亡，从而在口腔癌发生过程中引起极早期的免疫抑制反应，因此免疫抑制和肿瘤发展是相关的。 coevolved.版权所有 © 2023 Sahu、Thakur、Peroumal、Utkalaja、Dutta、Kumari、Subhadarsini 和 Acharya。

4-Nitroquinoline N-oxide (4-NQO) and its derivatives react with genomic DNA to form stable quinolone monoadducts, which are highly mutagenic and genotoxic. While the chronic high-dose exposure of epithelial cells to a carcinogen such as 4-NQO leads to tumor development, its effect on other cells has not been explored yet. Since the immunosuppression due to aberrant immunological profile is recognized as a significant cause in tumors, here we determine the interaction between 4-NQO and immune cells both in vivo and in vitro, and its effect on oral squamous cell carcinoma (OSCC) progression in a murine model. Immune cell profiling of the spleen and peripheral blood revealed a significant decrease in the B-cell population in 4-NQO-exposed mice than the untreated group. Additionally, γδ T and CD5+ B lymphocyte populations decreased at both pre- and post-cancerous stages of OSCC. These results suggested that 4-NQO induced tumor transition from pre-malignant lesions to OSCC by altering certain immune cells systemically. Next, to establish the effect of 4-NQO on immune cells, human B- and T-cell lines were subjected to 4-NQO; the reduction in cell viability, increase in DNA damage response marker, and induction of apoptosis were more pronounced in B than T cells. Altogether, our results indicated that in addition to the genotoxicity of oral epithelial cells, 4-NQO potentiates long-range effects on specific immune cells to induce cell death to cause very-early immunosuppressive response during oral carcinogenesis, and thus immunosuppression and tumor development are coevolved.Copyright © 2023 Sahu, Thakur, Peroumal, Utkalaja, Dutta, Kumari, Subhadarsini and Acharya.