P. Mccloskey et al., Resistance of three immortalized human hepatocyte cell lines to acetaminophen and N-acetyl-p-benzoquinoneimine toxicity, J HEPATOL, 31(5), 1999, pp. 841-851
Background/Aims: Acetaminophen toxicity in hepatocytes is attributed to gen
eration of the toxic metabolite N-acetyl-p-benzoquinoneimine, leading to de
pletion of intracellular glutathione, alteration of redox potential and ult
imately, cellular necrosis, We aimed to determine the effect of acetaminoph
en and N-acetyl-p-benzoquinoneimine on three human hepatocyte cell lines HH
25, HH29 and HHY41, and for comparison, on primary rat hepatocytes, a cell
type that is relatively resistant to acetaminophen-induced toxicity,
Methods; We investigated the effect of incubation of rat hepatocytes and 3
hepatocyte cell lines with acetaminophen or N-acetyl-p-benzoquinoneimine on
LDH release, glutathione status, mitochondrial function, CYP1A activity, a
lbumin synthesis and DNA content,
Results: We demonstrated that HH25, HH29 and HHY41 are resistant to the tox
ic effects of acetaminophen under conditions that induce cytotoxicity in ra
t primary hepatocytes, as indicated by maintenance of glutathione levels an
d basal LDH release, Incubation with N-acetyl-p-benzoquinoneimine caused a
dose-dependent cytotoxicity in rat hepatocytes, Under comparable conditions
N-acetyl-p-benzoquinoneimine had no effect on any of the hepatocyte cell l
ines, Nevertheless, when culturing the cells for a further 48 h, a decrease
in glutathione levels, albumin synthesis, CYP1A activity, DNA content and
mitochondrial function was apparent,
Conclusion: HH25, HH29 and HHY41 cells are highly resistant to acetaminophe
n and N-acetyl-p-benzoquinoneimine-induced toxicity. They tolerate a much h
igher concentration of both toxins for a longer period of time compared to
rat primary hepatocytes. These results are of relevance in the use df these
cell lines to investigate acetaminophen hepatotoxicity, and may be of impo
rtance in the choice of cells for use in bioartificial liver support system
s.