The transformics assay: first steps for the development of an integrated approach to investigate the malignant cell transformation in vitro

Abstract

The transformics method was developed to support the integrated testing strategy for carcinogenesis. Results showed the main role of the immune system in the transformation by 3-MCA, with initiating events related to non-genotoxic mechanisms, suggesting the involvement of the AhR receptor.

Genome‐wide DNA methylation changes in transformed foci induced by nongenotoxic carcinogens

“…Thus, in order to improve the use of this assay in an IATA for carcinogenesis, we developed a method combining the in vitro CTA and next‐generation sequencing‐based DNA methylation profiling analysis (MBD‐Seq) to elucidate the molecular steps leading to in vitro malignant transformation. In an approach similar to that in our study, Mascolo et al [] developed the transformics method, which combines the in vitro CTA and transcriptomics. In this study, the in vitro Bhas 42 CTA was performed with three nongenotoxic carcinogens (cadmium chloride, methyl carbamate, and lithocholic acid) whose genotoxicity and carcinogenicity have been confirmed in a wide range of test systems.…”

The Secretive Liaison of Particulate Matter and SARS-CoV-2. A Hypothesis and Theory Investigation

“…On the basis of our results, we speculated that the binding of PM components, such as PAHs, to the Aryl hydrocarbon Receptor (AhR) triggers an immune-mediated response, leading to the activation of molecular pathways sustaining inflammation, through the release of several cytokines as signal mediators (Mascolo et al, 2018). Cytokines play a key role in the innate immune response against pathogens or toxic substances and have a complex regulatory effect on the inflammation and immune system.…”

“…The toxicological properties increase linearly with increase in the PAHs concentration. Low concentrations trigger detoxification pathways, whilst higher concentrations activate an aberrant immune response, leading to genomic instability (Colacci et al, 2014;Vaccari et al, 2015;Mascolo et al, 2018;Serra et al, 2019). The entire process is orchestrated by the AhR.…”

“…It is the molecular target for dioxins, dioxin-like chemicals as well as PAHs, mediating the metabolic activation of xenobiotics and the response to environmental exposures. The complex AhR-ARNT binds specific DNA sequences, triggering the AhR signaling pathway, which leads to the transcription of the CYP1A1 and CYP1B1 genes, whose proteins play the main role in the bioactivation of several xenobiotics (Mascolo et al, 2018). The AhR is the only PAS protein that is activated by the ligand.…”

“…We have also found that the toxicological behavior of PM was strictly related to the content of PM components, such as the polycyclic aromatic hydrocarbons (PAHs). Indeed, PM can induce cell malignant transformation in vitro only when the concentration of PAHs exceeds the cells ability to implement its adaptive or detoxicant response (Vaccari et al, 2015;Mascolo et al, 2018;Serra et al, 2019).…”