Mechanism of cellular damages caused by cholorophenol compounds and their prevention

五氯苯酚(PCP)增加大鼠肝脏线粒体的耗氧量，降低线粒体的呼吸控制率(J UOEH 20：315,1998)。这些作用可被L肉碱所抑制，但不能被戊四氮所抑制。我们的其他发现包括：N-乙酰半胱氨酸抑制镉对LLC-PK1细胞的细胞毒性(J Pharmacol Exp Therap 287：344,1998)；镉激活的c-jun N末端激酶(JNX)在同一细胞中(Biochem Biphys Commun 251：527,1998)；肉碱抑制PTZ诱导的小鼠脑内c-fos的表达(J occup Health，出版社)；镉对缺乏c-fos的成纤维细胞的毒性更大(Biochem Pharmacol，出版社)。然而，缺乏c-fos的细胞对PCP和六氯酚(HCP)的反应与对照组没有明显差异。PCP和HCP均未引起JNK、ERK和p-38的明显激活，提示c-Fos和c-Jun的信号转导系统可能不参与上述氯酚类化合物的细胞毒性作用。然而，L肉碱可能减轻五氯苯酚对线粒体的毒性。

Pentachloropheno1 (PCP) increased oxygen consumption and decreased repiratory control ratio in mitochondria from rat liver (J UOEH 20:315, 1998). These effects of PCP were suppressed by L-carnitine but those of pentylenetetrazol (PTZ) were not. Other findings of ours include ; N-acetylcysteine suppressed cytotoxicity of cadmium in LLC-PK1 cells (J Pharmacol Exp Therap 287:344, 1998) ; cadmium activated c-Jun N-terminal kinase (JNX) in the same cells (Biochem Biphys Res Commun 251:527, 1998) ; carnitine suppressed PTZ-induced c-fos expression in the mouse brain (J Occup Health, in press) ; toxicity of cadmium was greater in fibroblasts lacking c-fos (Biochem Pharmacol, in press). Nevertheless, cells lacking c-fos showed no definite difference from the controls in response to PCP and hexachlorophene (HCP). Neither PCP nor HCP caused clear activation of JNK, ERK and p-38, suggesting that signal transduction system to c-Fos and c-Jun may not be involved in inducing cellar toxicity of above chlorophenol compounds. However, it is likely that toxicity of PCP on mitochondria may be lessened by L-carnitine.