Different roles of 8-hydroxyguanine formation and 2-thiobarbituric acid-reacting substance generation in the early phase of liver carcinogenesis induced by a choline-deficient, L-amino acid-defined diet in rats.
The present study was performed to assess the roles of hepatocellular oxidative damage to DNA and constituents other than DNA in rat liver carcinogenesis caused by a choline-deficient, L-amino acid-defined (CDAA) diet by examining the effects of the antioxidant N,N'-diphenyl-p-phenylenediamine (DPPD). The parameters used for cellular oxidative damage were the level of 8-hydroxy-guanine (8-OHGua) for DNA and that of 2-thiobarbituric acid-reacting substance (TBARS) for constituents other than DNA. A total of 40 male Fischer 344 rats, 6 weeks old, were fed the CDAA diet for 12 weeks with or without DPPD (0.05, 0.10 or 0.20%) or butylated hydroxytoluene (BHT, 0.25%). In the livers of the rats, the numbers and sizes of glutathione S-transferase (EC 2.5.1.18) placental form (GSTP)- and/or gamma-glutamyltransferase (GGT, EC 2.3.2.2)-positive lesions and levels of 8-OHGua and TBARS were determined. The GSTP-positive lesions of 0.08 mm2 or larger were all stained positively for GGT as well in cross-sectional area, whereas the smaller lesions were generally negative for GGT. DPPD and BHT reduced the size of the GSTP-positive lesions without affecting their total numbers. At the same time, they reduced TBARS generation without affecting 8-OHGua formation in DNA. The present results indicate that oxidative DNA damage (represented by 8-OHGua formation) and damage to constituents other than DNA (represented by TBARS generation) may play different roles in rat liver carcinogenesis caused by the CDAA diet; the former appears to be involved in the induction of phenotypically altered hepatocyte populations while the latter may be related to the growth of such populations.
Nakae
D
D
Department of Oncological Pathology, Nara Medical University.
Mizumoto
Y
Y
Yoshiji
H
H
Andoh
N
N
Horiguchi
K
K
Shiraiwa
K
K
Kobayashi
E
E
Endoh
T
T
Shimoji
N
N
Tamura
K
K
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002796:Choline Deficiency / Q000378:metabolism*; D004249:DNA Damage; D004032:Diet; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism*; D008297:Male; D010655:Phenylenediamines / Q000494:pharmacology*; D011230:Precancerous Conditions / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism*
D000975:Antioxidants; D010655:Phenylenediamines; D017392:Thiobarbituric Acid Reactive Substances; C024829:8-hydroxyguanine; D006147:Guanine; C004845:N,N'-diphenyl-4-phenylenediamine