Influence of the mycotoxins α- and β-zearalenol and deoxynivalenol on the cell cycle of cultured porcine endometrial cells

The present study investigated the effects of the mycotoxins alpha-zearalenol (alpha-ZOL) and beta-zearalenol (beta-ZOL) at concentrations of 7.5, 15, and 30 muM, and deoxynivalenol (DON) at concentrations of 0.94, 1.88, and 3.76 muM on cell cycle distribution (propidium iodide, PI staining) in combination with the proliferating cell nuclear antigen (PCNA) by flow cytometry. The viability of porcine uterine cells was not impaired at 30 muM alpha-ZOL, whereas beta-ZOL at this concentration and 3.76 muM DON significantly decreased cell number. Some cells showed ultrastructural features of cell death indicated by swollen mitochondria, disrupted cell membranes, and many vacuoles. After 24 and 48 h of exposure to alpha-ZOL (7.5, 15, or 30 muM), the cell cycle distribution was still comparable to the control groups. An anti-proliferative effect of beta-ZOL and DON was detected by a significant reduction in the S-phase together with arrest of cells in the G(0)/G(1)-phase. The results show that beta-ZOL (7.5, 15, or 30 muM) and DON (0.94, 1.88, or 3.76 muM) control the progression of cells through the cycle by decreasing S-phase and arresting cells in the G(0)/G(1)-phase of the cell cycle. A significant decrease in the expression of the proliferation marker PCNA amounts indicates that beta-ZOL and DON disengaged cells from active cycling. We confirm that alpha-ZOL possesses a relative binding affinity to porcine uterine cytoplasmic estrogen receptor. (C) 2003 Elsevier Science Inc. All rights reserved.