Mechanisms of Cd and Cu induced toxicity in human gastric epithelial cells: Oxidative stress, cell cycle arrest and apoptosis.

Cadmium (Cd) and copper (Cu) are widely present in foods. However, their adverse effects on human gastric epithelium are not fully understood. Here, human gastric epithelial cells (SGC-7901) were employed to study the toxicity and associated mechanisms of Cd + Cu co-exposure. Their effects on cell viability, morphology, oxidative damage, cell cycle, apoptosis, and the mRNA levels of antioxidases and cell cycle regulatory genes were investigated. Co-exposure to Cd (5 µM)/Cu (10 µM) induced >40% cell viability loss, whereas little effect on cell viability at <10 µM Cd or 40 µM Cu. Compared to individual exposure, co-exposure induced greater oxidative damage by elevating ROS (3.5 folds), malondialdehyde (2.3 folds) and expression of SOD1 and HO-1 besides inhibiting CAT, GPX1 and Nrf2. A marked S cell-cycle arrest was observed in co-exposure, evidenced by more cells staying in the S phase (36%), up-regulation of cyclins-dependent kinase (CDK4) and CDKs inhibitor (p21) and down-regulation of CDK2, CDK6 and p27. Furthermore, higher apoptosis (22%) with floated and round cells occurred in co-exposure group. Our data implicate the cytotoxicity of Cd + Cu co-exposure was higher than individual exposure, and individual assessment would underestimate their potential health risk. Oxidative stress and cell cycle arrest possibly played a role in Cd + Cu induced toxicity and apoptosis in SGC-7901 cells. Our data suggest the importance to reduce Cd in foods to decrease its adverse impacts on human digestive system.

Organophosphorus flame retardant TDCPP-induced cytotoxicity and associated mechanisms in normal human skin keratinocytes.

Tris(1,3-dichloro-2-propyl) phosphate (TDCPP), a widely used organophosphorus flame retardant, has been frequently detected in the environment including indoor dust. Long-term exposure to TDCPP-containing dust may adversely affect human skin, however, little is known about its potential cytotoxicity. In this study, human skin keratinocytes (HaCaT) were employed to study TDCPP-induced cytotoxicity and associated mechanisms. The effects of TDCPP on cell morphology, viability, apoptosis, and cycle, and the mRNA levels of apoptosis (Bcl-2, Bax and Caspase-3) and cell cycle (cyclin D1, CDK2, CDK4 and CDK6) regulatory genes were investigated. The results showed that TDCPP caused a concentration-dependent decrease in cell viability after exposing to TDCPP ≥100 µg/mL for 48 h, with a median lethal concentration of 163 µg/mL (LC50). In addition, TDCPP induced cell apoptosis and arrested cell cycle in the G0/G1 phase at 16 and 160 µg/mL by enhancing Bax and Caspase-3 expression besides inhibiting cyclin D1, CDK2, CDK6 and Bcl-2 expression. Our results showed that TDCPP-induced toxicity in HaCaT cells was probably through cell apoptosis and cell cycle arrest. This study provides information on the toxicity of TDCPP to human skin cells, which may help to reduce its toxicity to human skin.

Water extract of indoor dust induces tight junction disruption in normal human corneal epithelial cells.

In corneal epithelium, tight junctions play a vital role in its barrier function. Human cornea is highly susceptible to damage by dust. Continued daily exposure to dust has been associated with increased risks of corneal injury. Studies demonstrated that water extract of dust induced cytotoxicity in human corneal epithelial cells (HCECs); however, its effects on corneal epithelial barrier function are unknown. In this study, we determined the concentrations of heavy metals in water extracts of dust, with office dust having higher concentrations of heavy metals than housedust, and Cu and Zn being highest among metals for both dust. Changes in barrier function and its associated mechanism after exposing HCECs to water extracts of dust at 48 µg/100 µ L for 7 d were evaluated. Water extracts of both dust caused decrease of TEER value (39-73%), down-regulation of gene expression related to tight junction and mucin (0.2-0.8 fold), and loss of ZO-1 immunoreactivity from cellular borders, with office dust having greater potential than housedust to disrupt corneal epithelial barrier function. Our data implied the importance to reduce heavy metals in dust to reduce their adverse impacts on human eyes.