黃麴毒素B1致害大鼠肝細胞：核酸毒性及細胞凋亡引發相關性之探討

本研究以黃麴毒素B1 (AFB)腹腔注射大鼠72小時後，應用單細胞電泳法可在以0.25、0.5、1 mg/kg等非致死劑量AFB1處理後之細胞，檢出呈現顯著濃度效應之DNA單股斷裂。且細胞族群在各濃度處理下呈現個體差異性的DNA損壞。在2 mg/kg的AFB1處理下，大鼠肝臟呈現亞急性至急性肝炎反應，且伴隨膽管增生及少量典型細胞凋亡(apoptosis)之病變，而致死劑量5 mg/kg AFB1處理下，則有出血、大區域肝細胞壞死等嚴重急性肝炎病變以及典形細胞凋亡之形態學變化；電泳法則呈現肝細胞DNA則出現輕微185 bps規則斷裂現象。TUNEL染色結果顯示5mg/kg AFB1處理組之肝組織病理切片，多出現明顯陽性細胞凋亡之反應。各AFB1處理組之p53及Bcl-2蛋白表現，則無法檢出。本研究結果顯示高劑量AFB1對肝細胞同時造成以壤死及細胞凋亡病變形式死亡而低劑量AFB1對肝細胞具有基因毒害之效果。p53及Bcl-2在AFB1致害機制則尚待決定。

關鍵字

黃麴毒素B1 ；肝細胞；細胞凋亡； DNA單股斷裂

並列摘要

single strand breaks and apoptosis in AFB1-induced cytotoxicities in rat hepatocytic cells were investigated. Hepatocytes collected from rat exposed to 0.25, 0.5 and 1.0 mg/kg AFB for 72 hours in vivo showed significant increases (p＜0.05) in DNA single strand breaks in a dosage-dependent pattern. Individual difference in the induction of DNA strand breaks in a cell population that received the same AFB1 treatment also could be observed. At higher dosage, 2.0 mg/kg AFB1 treatment elicited sub-acute to acute hepatitis accompanied with hyperplasia in bile duct epithelia. In addition, with lethal dosage (5.0 mg/kg), diffused necrosis, hemorrhage, inflammation, and apoptosis could be found in rat exposed to AFB1 Characteristic morphological changes in apoptotic hepatocytes were confirmed by TUNNEL assay, TEM and by the appearance of 185-200 bps DNA fragmentation. Expression of p53 and Bcl-2 proteins could not be quantified by western `blot analysis in all treatments. We concluded that apoptosis and/or necrosis in rat hepatocytes could be the consequences of AFB1 exposure at higher dosage range and nucleic DNA damages resulted from lower AFB1 dosage range. The role of Bcl-2 and p53 in AFB1 toxicities remains to be determined.

並列關鍵字

Aflatoxin B1 ； Hepatocyte ； DNA Single Strand Breaks ； Apoptosis

國際替代計量

黃麴毒素B1致害大鼠肝細胞：核酸毒性及細胞凋亡引發相關性之探討

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