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Background and objective Metabolic change is one of the important characteristics of radiation pneumonitis. Radiotherapy, as a conventional method for the treatment of thoracic tumors, can not only effectively kill tumor cells, but also cause adverse reactions such as local inflammation and fibrosis, which leads to limited therapeutic effect and profound impact on the quality of life of patients. Therefore, it is of great significance to explore the metabolic changes caused by radio-therapy. The aim of this study was to investigate the effects of X-ray irradiation on the metabolism of a mouse lung epithelial cell line (murine lung epithelial-12, MLE12). Methods MLE12 cells were cultured in vitro and randomly divided into radiation group (IR) and control group (NC). Cells in the IR group were irradiated at a dose of 10 Gy using a Hitachi X-ray irradiator. Cell supernatant samples were collected at 48 h after irradiation. Metabolomic analysis of the samples was performed by liquid chromatograph mass spectrometer (LC/MS). Results LC/MS metabolomics analysis revealed the metabolic changes of MLE12 cells at 48 h after irradiation. A total of 38 secretory metabolites were altered in the IR group compared with the NC group. According to the annotation of Kyoto Encyclopedia of Genes and Genomes (KEGG) database, the differential metabolites are mainly involved in nucleotide metabolism, amino acid metabolism and lipid metabolism, among which the difference in nucleotide metabolism is the most significant. Conclusion The metabolism of MLE12 cells was significantly affected by X-ray irradiation, mainly affecting the nucleotide metabolic pathways, including purine and pyrimidine metabolites and related metabolic pathways. [ABSTRACT FROM AUTHOR]

P53 is a key factor encoded by the TP53, and it prevents cells from becoming cancerous and has a wide range of powerful functions. p53 is found to play an important role in inducing DNA repair, apoptosis, cell cycle arrest and senescence, and the loss of these functions does not abrogate P53’s tumor suppressive activity. Metabolism is the basis of life, and metabolic abnormalities can lead to a variety of diseases, including tumors, and is one of the main drivers of cancer progression. It has recently been discovered that P53 plays a key role in regulating metabolism. P53-mediated regulation of cell metabolism is a fundamental mechanism controlling cancer occurrence and development and contributes to its tumor suppressive activity. Here, this article reviewed the relationship between P53 and glucose, fatty acid, amino acid and nucleotide metabolism, and discussed the complex mechanism and the latest research progress of P53 in the metabolic regulation in tumor development.

P53 is a key factor encoded by the TP53, and it prevents cells from becoming cancerous and has a wide range of powerful functions. p53 is found to play an important role in inducing DNA repair, apoptosis, cell cycle arrest and senescence, and the loss of these functions does not abrogate P53's tumor suppressive activity. Metabolism is the basis of life, and metabolic abnormalities can lead to a variety of diseases, including tumors, and is one of the main drivers of cancer progression. It has recently been discovered that P53 plays a key role in regulating metabolism. P53-mediated regulation of cell metabolism is a fundamental mechanism controlling cancer occurrence and development and contributes to its tumor suppressive activity. Here, this article reviewed the relationship between P53 and glucose, fatty acid, amino acid and nucleotide metabolism, and discussed the complex mechanism and the latest research progress of P53 in the metabolic regulation in tumor development. [ABSTRACT FROM AUTHOR]

Background: Metabolic change is one of the important characteristics of radiation pneumonitis. Radiotherapy, as a conventional method for the treatment of thoracic tumors, can not only effectively kill tumor cells, but also cause adverse reactions such as local inflammation and fibrosis, which leads to limited therapeutic effect and profound impact on the quality of life of patients. Therefore, it is of great significance to explore the metabolic changes caused by radiotherapy. The aim of this study was to investigate the effects of X-ray irradiation on the metabolism of a mouse lung epithelial cell line (murine lung epithelial-12, MLE12)., Methods: MLE12 cells were' cultured in vitro and randomly divided into radiation group (IR) and control group (NC). Cells in the IR group were irradiated at a dose of 10 Gy using a Hitachi X-ray irradiator. Cell supernatant samples were collected at 48 h after irradiation. Metabolomic analysis of the samples was performed by liquid chromatograph mass spectrometer (LC/MS)., Results: LC/MS metabolomics analysis revealed the metabolic changes of MLE12 cells at 48 h after irradiation. A total of 38 secretory metabolites were altered in the IR group compared with the NC group. According to the annotation of Kyoto Encyclopedia of Genes and Genomes (KEGG) database, the differential metabolites are mainly involved in nucleotide metabolism, amino acid metabolism and lipid metabolism, among which the difference in nucleotide metabolism is the most significant., Conclusions: The metabolism of MLE12 cells was significantly affected by X-ray irradiation, mainly affecting the nucleotide metabolic pathways, including purine and pyrimidine metabolites and related metabolic pathways.

Deoxycytidine triphosphate pyrophosphatase 1(dCTP pyrophosphatase 1, DCTPP1) is a newly discovered pyrophosphatase targeting deoxycytidine triphosphate (dCTP). It regulates cytosine metabolism by not only hydrolyzing conventional and modified dCTP, but also participating in the steady-state regulation of other pyrimidine nucleotides. In the process of tumor cells, the high expression of DCTPP1 is facilitate to stabilize the balance of deoxynucleoside triphosphate pool (dNTP pool),methylation of the genome, and maintainance of stability of the tumor cell genome. Besides, DCTPP1 promotes malignant phenotypes such as tumor cell proliferation and metastasis through different signal pathways, and it is related to tumor drug resistance and poor clinical prognosis. DCTPP1 may become a “star” target for the development of anti-tumor drugs. In-depth research on its regulatory mechanism is expected to provide a new strategy for the development of targeted inhibitors of tumor nucleotide metabolism.

Short-chain chlorinated paraffins (SCCPs) are an emerging class of persistent organic pollutants (POPs) that are widely detected in environmental matrices and human samples. Because of their environmental persistence, long-range transport potential, bioaccumulation potential, and biotoxicity, SCCPs pose a significant threat to human health. In this study, metabolomics technology was applied to reveal the metabolomic interference in human normal hepatic (L02) cells after exposure to low (1 μg/L), moderate (10 μg/L), and high (100 μg/L) doses of SCCPs. Principal component analysis (PCA) and metabolic effect level index (MELI) values showed that all three SCCP doses caused notable metabolic perturbations in L02 cells. A total of 72 metabolites that were annotated by MS/MS and matched with the experimental spectra in the Human Metabolome Database (HMDB) or validated by commercially available standards were selected as differential metabolites (DMs) across all groups. The low-dose exposure group shared 33 and 36 DMs with the moderate- and high-dose exposure groups, respectively. The moderate-dose exposure group shared 46 DMs with the high-dose exposure group. In addition, 33 DMs were shared among the three exposure groups. Among the 72 DMs, 9, 9, and 45 metabolites participated in the amino acid, nucleotide, and lipid metabolism pathways, respectively. The results of pathway enrichment analysis showed that the most relevant metabolic pathways affected by SCCPs were the lipid metabolism, fatty acid β-oxidation, and nucleotide metabolism pathways, and that compared with low-dose exposure, moderate- and high-dose SCCP exposures caused more notable perturbations of these metabolic pathways in L02 cells. Exposure to SCCPs perturbed glycerophospholipid and sphingolipid metabolism. Significant alterations in the levels of phosphatidylcholines, phosphatidylethanolamines, and sphingomyelins indicated SCCP-induced biomembrane damage. SCCPs inhibited fatty acid β-oxidation by decreasing the levels of short- and medium-chain acylcarnitines in L02 cells, indicating that the energy supplied by fatty acid oxidation was reduced in these cells. Furthermore, compared with low- and moderate-dose SCCPs, high-dose SCCPs produced a significantly stronger inhibition of fatty acid β-oxidation. In addition, SCCPs perturbed nucleotide metabolism. The higher hypoxanthine levels observed in L02 cells after SCCP exposures indicate that SCCPs may induce several adverse effects, including hypoxia, reactive oxygen species production, and mutagenesis in L02 cells.