Serum DNA polymerase beta as an indicator for fatal liver injury of rat induced by D-galactosamine hydrochloride and lipopolysaccharide.
DNA polymerase beta (pol beta) is a nuclear enzyme that is tightly bound to chromatin. Release of the pol beta activity into serum, therefore, may indicate the occurrence of massive destruction of cell nuclei in organs or tissues. In the present study, we made a liver injury model rat by the intraperitoneal injection of D-galactosamine hydrochloride (GalN, 500 mg/kg) and lipopolysaccharide (LPS, 100 microg/kg). Serum from the GalN/LPS-treated rats showed a high level of pol beta activity up to 118 pmol/0.5 microl serum (4700 cpm) at 12 h after the treatment, while the control rat serum showed the back ground level (3.8 pmol/0. 5 microl, 150+/-70 cpm). The serum pol beta activity was sensitive to inhibition by 2',3'-dideoxyTTP and by an anti-rat pol beta antibody. Among 30 rats treated with GalN/LPS, 10 rats died within 120 h (dead group). Serum pol beta activity in the dead group was as high as 23.0+/-19.5 pmol/0.5 microl (925+/-778 cpm) at 10 h after the treatment, while in alive group (n=20), it was 3.7+/-3.2 pmol. Levels of the serum pol beta activity correlated well with the prognosis of GalN/LPS-treated rats based on an analysis of the receiver-operator characteristic curves.
Kato
O
O
Second Department of Internal Medicine, Nagoya University School of Medicine, Showa-ku, Nagoya, 466-8550, Japan.
Fukuda
Y
Y
Hayakawa
T
T
Izuta
S
S
Yoshida
S
S
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D015415:Biomarkers / Q000097:blood; D019951:DNA Polymerase beta / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D005688:Galactosamine / Q000633:toxicity*; D006501:Hepatic Encephalopathy / Q000097:blood / Q000139:chemically induced / Q000201:enzymology*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008099:Liver / Q000201:enzymology / Q000473:pathology*; D008297:Male; D011237:Predictive Value of Tests; D011379:Prognosis; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D015415:Biomarkers; D008070:Lipopolysaccharides; D005688:Galactosamine; D000410:Alanine Transaminase; D019951:DNA Polymerase beta