Phosphorylation of eIF2α promotes cell survival in response to benzo[a]pyrene exposure.

Cellular adaptation is important to cope with various stresses induced by altered environmental conditions. By controlling mRNA translation rates cells may adapt to stress to promote survival. Phosphorylation of eIF2α at serine 51 is one of the pathways controlling mRNA translation.

Translational regulation is a key determinant of the cellular response to benzo[a]pyrene.

Translational control is a cellular response mechanism which initiates adaptation during various stress situations. Here, we investigated the role of translational control after benzo[a]pyrene (BaP) exposure in primary mouse hepatocytes. Translated mRNAs were separated and captured based on the number of associated ribosomes using sucrose gradients and subjected to RNA sequencing (RNAseq) to investigate translational changes.

Decitabine, a DNA-demethylating agent, promotes differentiation via NOTCH1 signaling and alters immune-related pathways in muscle-invasive bladder cancer.

Aberrant DNA methylation observed in cancer can provide survival benefits to cells by silencing genes essential for anti-tumor activity. DNA-demethylating agents such as Decitabine (DAC)/Azacitidine (AZA) activate otherwise silenced tumor suppressor genes, alter immune response and epigenetically reprogram tumor cells. In this study, we show that non-cytotoxic nanomolar DAC concentrations modify the bladder cancer transcriptome to activate NOTCH1 at the mRNA and protein level, increase double-stranded RNA sensors and CK5-dependent differentiation.

Identification of essential transcription factors for adequate DNA damage response after benzo(a)pyrene and aflatoxin B1 exposure by combining transcriptomics with functional genomics.

DNA damage mediates widespread changes in transcription through activation or repression of transcription factors (TFs). However, the consequences of regulating specific TFs for the outcome of the DNA repair process remain incompletely understood. Here, we combined transcriptomics and TF binding prediction with functional genomics to identify TFs essential for adequate DNA repair in HepG2 liver cells after a non-cytotoxic dose of carcinogens benzo(a)pyrene (BaP) (2μM) and aflatoxin B1 (AFB1) (5μM).

The radiosensitizing effect of fluorocyclopentenyl-cytosine (RX-3117) in ovarian and lung cancer cell lines.

RX-3117 (fluorocyclopentenyl-cytosine) is a novel cytidine analog currently being evaluated in a Phase Ib clinical trial in cancer patients with solid tumors. The radiosensitizing effect of RX-3117 was studied in A2780 ovarian cancer cells and non-small cell lung cancer cell lines and related to cell survival and the effect on cell cycle and cell cycle proteins. RX-3117 has a schedule-dependent radiosensitizing effect, but only at pre-incubation (dose modifying factors: 1.