Dose-dependent induction of 8-hydroxyguanine and preneoplastic foci in rat liver by a food-derived carcinogen, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, at low dose levels.
Male F344 rats were administered 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) in the diet at doses of 200, 50, 12.5, 3.2, 0.8, 0.2 and 0.05 ppm for six weeks, and partially hepatectomized 1 week after the beginning of MeIQx administration. Quantitative values for glutathione S-transferase placental form (GST-P)-positive foci in the liver were dose-dependently increased by the MeIQx treatment. 8-Hydroxyguanine (8-OHG) levels assessed after 1 week of dietary MeIQx administration were also dose-dependently increased, although the effect was no longer observed at the end of the treatment period. The correlation between numbers of GST-P-positive foci at week 6 and 8-OHG levels at week 1 was linear, values for both parameters being higher than the control levels even in the 0.8 ppm dose group. These findings indicate that, in addition to the previously reported MeIQx-DNA adduct formation, DNA modifications due to oxidative damage may play an important role in MeIQx liver carcinogenesis in rats.
Kato
T
T
First Department of Pathology, Nagoya City University Medical School, Japan.
Hasegawa
R
R
Nakae
D
D
Hirose
M
M
Yaono
M
M
Cui
L
L
Kobayashi
Y
Y
Konishi
Y
Y
Ito
N
N
Shirai
T
T
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens; D004032:Diet; D005982:Glutathione Transferase / Q000378:metabolism; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism; D008099:Liver / Q000033:anatomy & histology; D008113:Liver Neoplasms / Q000139:chemically induced*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011230:Precancerous Conditions / Q000139:chemically induced*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344
D002273:Carcinogens; D011810:Quinoxalines; C024829:8-hydroxyguanine; D006147:Guanine; C036990:2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline; D005982:Glutathione Transferase