Industrial-relevant TiO2 types do not promote cytotoxicity in the A549 or TK6 cell lines regardless of cell specific interaction.

Due to the expansive application of TiO2 and its variance in physico-chemical characteristics, the toxicological profile of TiO2, in all its various forms, requires evaluation. This study aimed to assess the hazard of five TiO2 particle-types in relation to their cytotoxic profile correlated to their cellular interaction, specifically in human lymphoblast (TK6) and type-II alveolar epithelial (A549) cells. Treatment with the test materials was undertaken at a concentration range of 1-100 µg/cm2 over 24 and 72 h exposure. TiO2 interaction with both cell types was visualised by transmission electron microscopy, supported by energy-dispersive X-ray. None of the TiO2 materials tested promoted cytotoxicity in either cell type over the concentration and time range studied. All materials were observed to interact with the A549 cells and were further noted to be internalised following 24 h exposure. In contrast, only the pigmentary rutile was internalised by TK6 lymphoblasts after 24 h exposure. Where uptake was observed there was no evidence, as determined by 2D microscopy techniques, of particle localisation within the nucleus of either cell type. This study indicates that industrially relevant TiO2 particles demonstrate cell interactions that are cell-type dependent and do not induce cytotoxicity at the applied dose range.

Developing a blood-based gene mutation assay as a novel biomarker for oesophageal adenocarcinoma.

The Phosphatidylinositol glycan class A (PIG-A) gene mutation assay phenotypically measures erythrocyte mutations, assessed here for their correlation to neoplastic progression in the gastro-oesophageal reflux disease (GORD)-Barrett's metaplasia (BM)-oesophageal adenocarcinoma (OAC) model. Endoscopy patients underwent venipuncture and erythrocytes fluorescently stained for glycosyl phosphatidylinositol (GPI)-anchored proteins; CD55 and CD59. Using flow cytometry, GPI-anchor negative erythrocytes (mutants) were scored and compared amongst groups. The study enlisted 200 patients and 137 healthy volunteers. OAC patients had a three-fold increase in erythrocyte mutant frequency (EMF) compared to GORD patients (p < 0.001) and healthy volunteers (p < 0.001). In OAC patients, higher EMF was associated with worsening tumour staging (p = 0.014), nodal involvement (p = 0.019) and metastatic disease (p = 0.008). Chemotherapy patients demonstrated EMF's over 19-times higher than GORD patients. Patients were further classified into groups containing those with non-neoplastic disease and those with high-grade dysplasia/cancer with 72.1% of cases correctly classified by high EMF. Within the non-neoplastic group, aspirin users had lower EMF (p = 0.001) and there was a positive correlation between body mass index (p = 0.03) and age (p < 0.001) and EMF. Smokers had EMF's over double that of non-smokers (p = 0.011). Results suggest this test could help detect OAC and may be a useful predictor of disease progression.