Cellular biological study on mechanisms of acrylamide toxicity and its prevention

利用超高场磁共振（MR），我们发现丙烯酰胺（50 mg/kg/天，8天，i. p.）导致大鼠脑的形态学改变（脑室和脑池扩大，皮质变薄）。在此之前，我们表明，MR是一个非常强大的工具，以调查的变化，在大鼠大脑所造成的六氯环己烷。由于有报道丙烯酰胺可诱导小鼠脑中即刻早期基因c-Fos的表达，因此我们使用了一种有效的c-Fos诱导剂戊四氮（PTZ），发现PTZ可引起小鼠脑中c-Fos mRNA的增加，并且可被L-肉毒碱抑制。我们还发现，各种化学物质激活丝裂原活化蛋白激酶（MAPK），钙在某些情况下是重要的。在此基础上，我们研究了丙烯酰胺对人神经母细胞瘤SH/SY 5 Y细胞的影响。孵育48-72小时后，丙烯酰胺引起细胞毒性。而丙烯酰胺暴露没有引起c-Fos mRNA的显著增加，c-Jun mRNA增加。然而，没有发现MAPK（ERK，JNK，p38）的激活。

Utilizing ultra-high field magnetic resonance (MR), we found that acrylamide (50 mg/kg/day, 8 days, i.p.) causes morphological alterations in the rat brain (enlargement of ventricles and cisterns, thinning of cortex). Before this, we showed that MR is a very powerful tool to investigate changes in the rat brain caused by hexachlorophene. Since it was reported that acrylamide induced c-Fos, one of the immediate early genes, in the brain, we used pentylenetetrazol (PTZ), an established potent inducer of c-Fos, and found that PTZ causes increase of mRNA of c-Fos in the mouse brain and that it can be suppressed by L-carnitine. We also found that various chemicals activate mitogen activated protein kinase (MAPK) and that calcium is important in some cases. Based on these, we examined effects of acrylamide on human neuroblastoma SH/SY5Y cells. Acrylamide caused cell toxicity after incubation for 48-72 hours. Whereas it did not cause significant increase of c-Fos mRNA, exposure to acrylamide increased c-Jun mRNA. Nevertheless, no activation of MAPKs (ERK, JNK, p38) was found.