Molecular Mechanism of Malignant Transformation of Balb/c-3T3 Cells Induced by Long-Term Exposure to 1800 MHz Radiofrequency Electromagnetic Radiation (RF-EMR)

Abstract

Purpose: We aimed to investigate RF-EMR-induced cell malignant transformation. Methods: We divided Balb/c-3T3 cells into sham and expo groups. The expo groups were exposed to a 1800 MHz RF continuous wave for 40 and 60 days, for 4 h per day. The sham group was sham-exposed. Cells were harvested for a cell transformation assay, transplantation in severe combined immune deficient (SCID) mice, soft agar clone formation detection, and a transwell assay. The mRNA microarray assay was used to declare key genes and pathways. Results: The exposed Balb/c-3T3 cells showed a strong increase in cell proliferation and migration. Malignant transformation was observed in expo Balb/c-3T3 cells exposed for 40 days and 60 days, which was symbolized with visible foci and clone formation. Expo Balb/c-3T3 cells that were exposed for 40 days and 60 days produced visible tumors in the SCID mice. Lipid metabolism was the key biological process and pathway involved. The mevalonate (MVA) pathway was the key metabolic pathway. The interacted miRNAs could be further research targets to examine the molecular mechanism of the carcinogenic effects of long-term exposure. Conclusion: Exposure for 40 and 60 days to 1800 MHz RF-EMR induced malignant transformation in Balb/c-3T3 cells at the SAR of 8.0 W/kg. We declared that lipid metabolism was the pivotal biological process and pathway. The MVA pathway was the key metabolic pathway.

Mechanistic Interrogation of Cell Transformation In Vitro: The Transformics Assay as an Exemplar of Oncotransformation

“…It has been demonstrated that paracrine signaling from CAFs and myofibroblasts can regulate epithelial-mesenchymal plasticity, fibroblast activation, ECM modification and promote tumor progression and fibrosis [ 18 , 30 , 32 , 35 , 37 , 54 ].…”

“…Due to the complexity of events that together contribute to chemical carcinogenesis, it is unlikely that a single method will be able to provide enough information about diverse events/mechanisms of actions and possible interactions [ 9 , 10 , 11 ]. Particularly, several studies have combined cellular transformation experiments using different cell lines with the transcriptome profiling, in order to explore the malignant transformation process [ 10 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ].…”

“…Nowadays, the CTAs can be particularly attractive within the field of alternative methods for carcinogenicity due to their potential to detect both genotoxic and non-genotoxic carcinogens. Indeed, mechanistic cancer research has proposed several types of optimization of this assay [ 11 , 15 , 16 , 17 , 18 ]. There are multiple mechanisms of action of non-genotoxic carcinogens, far more so than for genotoxic carcinogens, which induce cancer by interacting directly with DNA and/or the cellular apparatus involved in the preservation of the integrity of the genome [ 10 , 20 ].…”