Enhancement of acetaminophen cytotoxicity in selenium-binding protein-overexpressed COS-1 cells.
The role of selenium-binding protein (SeBP), which has a high ability to associate with acetaminophen (AAP), on the cytotoxicity of AAP was studied. To clarify this issue, we examined the cytotoxic effect of AAP using COS cells stably expressing SeBP. Expression of SeBP enhanced the susceptibility of the cells to AAP-induced cytotoxicity. Several clones of SeBP-expressed COS cells were obtained, and they exhibited different degrees of susceptibility toward AAP. It was found that there is an inverse correlation between the expression level and the cell viability (r=-0.872). On the other hand, no increase in toxicity was observed in the SeBP-expressed cells treated with N-acetyl-p-quinone imine (NAPQI), which is an active metabolite of AAP. These results show that SeBP is an important factor in AAP hepatotoxicity. Moreover, our data suggest that the toxic mechanism of AAP differs from that of NAPQI.
Ishida
Takumi
T
Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Abe
Masamiki
M
Oguri
Kazuta
K
Yamada
Hideyuki
H
D000082:Acetaminophen / Q000633:toxicity*; D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002522:Chlorocebus aethiops; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D051137:Selenium-Binding Proteins
D002352:Carrier Proteins; D051137:Selenium-Binding Proteins; D000082:Acetaminophen