Li W, Riley R T, Voss K A, Norred W P
University of Georgia, Athens, Georgia, USA.
J Toxicol Environ Health A. 2000 Aug 11;60(7):441-57. doi: 10.1080/00984100050079511.
Fumonisin mycotoxins are common contaminants of maize and cause several fatal animal diseases. Liver is a target organ of fumonisins in intact animals, but liver slices and primary hepatocytes, which do not proliferate in culture, are resistant to fumonisin exposure. Hepatoma cell lines, on the other hand, undergo cell division in culture and are sensitive to the toxic effects of fumonisins. It was therefore hypothesized that fumonisin cytotoxicity is dependent on cell proliferation. To test this hypothesis, the partially hepatectomized rat was used as a model to determine whether fumonisin produced greater toxicity in rapidly proliferating liver in vivo. Rats were dosed intraperitoneally with fumonisin B1 (FB1) 24 h after sham operation or partial hepatectomy (PH) and were killed 24 h later. The dose-related increase in free sphingoid bases (a biomarker of fumonisin exposure) was enhanced in the PH-treated rats. Serum cholesterol and enzymes were higher in PH-treated rats dosed with FB1 than in those given PH without FB1 or in sham-operated, FB1-dosed rats. Multiple daily doses of FB1 after surgery elevated the number of apoptotic hepatocytes in both sham-operated and PH-treated rats to about the same degree, suggesting that apoptosis is not associated with the enhanced cytotoxicity of FB1 in regenerating liver. Proliferating cells appear to be more sensitive to the toxic effects of fumonisins. This enhanced cytotoxicity may be related to the increased ability of fumonisins to disrupt sphingolipid metabolism in hepatectomized rats, but this is yet to be determined.
伏马菌素类霉菌毒素是玉米常见的污染物，可引发多种致命的动物疾病。在完整动物体内，肝脏是伏马菌素的靶器官，但肝脏切片和原代肝细胞在培养过程中不增殖，对伏马菌素暴露具有抗性。另一方面，肝癌细胞系在培养中会进行细胞分裂，对伏马菌素的毒性作用敏感。因此，有人推测伏马菌素的细胞毒性取决于细胞增殖。为验证这一假设，以部分肝切除大鼠为模型，来确定伏马菌素在体内快速增殖的肝脏中是否产生更大的毒性。在假手术或部分肝切除（PH）24小时后，给大鼠腹腔注射伏马菌素B1（FB1），24小时后处死。在接受PH处理的大鼠中，游离鞘氨醇碱（伏马菌素暴露的生物标志物）与剂量相关的增加更为明显。与未注射FB1的PH处理大鼠或假手术且注射FB1的大鼠相比，注射FB1的PH处理大鼠血清胆固醇和酶水平更高。术后多次每日注射FB1，使假手术和PH处理大鼠的凋亡肝细胞数量升高到大致相同程度，这表明凋亡与FB1在再生肝脏中增强的细胞毒性无关。增殖细胞似乎对伏马菌素的毒性作用更敏感。这种增强的细胞毒性可能与伏马菌素扰乱肝切除大鼠鞘脂代谢能力的增加有关，但这还有待确定。
