Dual effects of N-acetyl-l-cysteine dependent on NQO1 activity: Suppressive or promotive of 9,10-phenanthrenequinone-induced toxicity

A typical antioxidant, N-acetyl-L-cysteine (NAC) generally protects cells from oxidative damage induced by reactive oxygen species (ROS). 9,10-Phenanthrenequinone (9,10-PQ), a major quinone in diesel exhaust particles, produces ROS in redox cycling following two-electron reduction by NAD(P)H:quinone oxidoreductase 1 (NQO1), which has been considered as a cause of its cyto- and genotoxicity. In this study, we show that NAC unexpectedly augments the toxicity of 9,10-PQ in cells with low NQO1 activity. In four human skin cell lines, the expression and the activity of NQO1 were lower than in human adenocarcinoma cell lines, A549 and MCF7. In the skin cells, the cytotoxicity of 9,10-PQ was significantly enhanced by addition of NAC. The formation of DNA double strand breaks accompanying phosphorylation of histone H2AX, was also remarkably augmented. On the other hand, the cyto- and genotoxicity were suppressed by addition of NAC in the adenocarcinoma cells. Two contrasting experiments: overexpression of NQO1 in CHO-K1 cells which originally expressed low NQO1 levels, and knock-down of NQO1 in the adenocarcinoma cell line A549 by transfection of RNAi, also showed that NAC suppressed 9,10-PQ-induced toxicity in cell lines expressing high NQO1 activity and enhanced it in cell lines with low NQO1 activity. The results suggested that dual effects of NAC on the cyto- and genotoxicity of 9,10-PQ were dependent on tissue-specific NQO1 activity

Calcification responses of symbiotic and aposymbiotic corals to near-future levels of ocean acidification

Increasing the acidity of ocean waters will directly threaten calcifying marine organisms such as reef-building scleractinian corals, and the myriad of species that rely on corals for protection and sustenance. Ocean pH has already decreased by around 0.1 pH units since the beginning of the industrial revolution, and is expected to decrease by another 0.2–0.4 pH units by 2100. This study mimicked the pre-industrial, present, and near-future levels of <i>p</i>CO₂ using a precise control system (± 5% <i>p</i>CO₂), to assess the impact of ocean acidification on the calcification of recently settled primary polyps of <i>Acropora digitifera</i>, both with and without symbionts, and adult fragments with symbionts. The increase in <i>p</i>CO₂ of ~100 μatm between the pre-industrial period and the present had more effect on the calcification rate of adult <i>A. digitifera</i> than the anticipated future increases of several hundreds of micro-atmospheres of <i>p</i>CO₂. The primary polyps with symbionts showed higher calcification rates than primary polyps without symbionts, suggesting that: (i) primary polyps housing symbionts are more tolerant to near-future ocean acidification than organisms without symbionts, and (ii) corals acquiring symbionts from the environment (i.e., broadcasting species) will be more vulnerable to ocean acidification than corals that maternally acquire symbionts