The effects of lairage time and handling procedure prior to slaughter on stress and meat quality parameters in pigs.

Lairage time (short - 8min to 2.7h, n=28 vs. long - 14 to 21.5h, n=72) and pig handling (gentle - no use of stick or electric prod, pig not slipping, falling, nor emitting high-pitched vocalizations vs. rough - where any of these occurred) effects on pig stress and meat quality were measured. Blood lactate and cortisol, plus post-mortem pH (pH60min; pH24h), temperature (T60min), drip loss, sensory and instrumental color and meat quality for the longissimus dorsi, pars lumbalis derived meat were determined. Carcass rigor mortis and skin damages were measured. Lairage time significantly affected blood lactate, carcass rigor mortis, skin damages, drip loss, color and meat quality. Handling procedure influenced blood lactate, pH60min and T60min. Long lairage was more stressful, and was detrimental to carcass quality, but caused better meat quality compared to short lairage. Rough handling was related to higher lactate and lower meat quality.

Role of thioredoxin in the response of normal and transformed cells to histone deacetylase inhibitors.

This study examines the basis of resistance and sensitivity of normal and transformed cells to histone deacetylase inhibitor (HDACi)-induced cell death, specifically the role of caspases and thioredoxin (Trx). An important attribute of HDACis is that they induce cancer cell death at concentrations to which normal cells are relatively resistant, making them well suited for cancer therapy. The mechanism underlying this selectivity has not been understood. In this study we found that the HDACi suberoylanilide hydroxamic acid (SAHA) and MS-275, a benzamide, cause an accumulation of reactive oxygen species (ROS) and caspase activation in transformed but not normal cells. Inhibition of caspases does not block HDACi-induced cell death. These studies provide a possible mechanism that can explain why normal but not certain transformed cells are resistant to HDACi-induced cell death. The HDACi causes an increase in the level of Trx, a major reducing protein for many targets, in normal cells but not in transformed cells. The SAHA-induced increase in Trx activity in normal cells is associated with no increase in ROS accumulation. Transfection of transformed cells with Trx small interfering RNA caused a marked decrease in the level of Trx protein with an increase in ROS, a decrease in cell proliferation, and an increase in sensitivity to SAHA-induced cell death. Thus, Trx, independent of the caspase apoptotic pathway, is an important determinant of resistance of cells to HDACi-induced cell death.

A senescence-like phenotype distinguishes tumor cells that undergo terminal proliferation arrest after exposure to anticancer agents.

Exposure of human tumor cell lines to different chemotherapeutic drugs, ionizing radiation, and differentiating agents induced morphological, enzymatic, and ploidy changes resembling replicative senescence of normal cells. Moderate doses of doxorubicin induced this senescence-like phenotype (SLP) in 11 of 14 tested cell lines derived from different types of human solid tumors, including all of the lines with wild-type p53 and half of p53-mutated cell lines. SLP induction seemed to be independent from mitotic cell death, the other major effect of drug treatment. Among cells that survived drug exposure, SLP markers distinguished those cells that became terminally growth-arrested within a small number of cell divisions from the cells that recovered and resumed proliferation. SLP induction in breast carcinoma cells treated with retinoids in vitro or in vivo was found to correlate with permanent growth inhibition under the conditions of minimal cytotoxicity, suggesting that this response may be particularly important for the antiproliferative effect of differentiating agents. The senescence-like program of terminal proliferation arrest may provide an important determinant of treatment outcome and a target for augmentation in cancer therapy.