Open AccessDose‐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
Author(s) -
Kato Toshio,
Hasegawa Ryohei,
Nakae Dai,
Hirose Masao,
Yaono Makoto,
Cui Lin,
Kobayashi Yozo,
Konishi Yoichi,
Ito Nobuyuki,
Shirai Tomoyuki
Publication year - 1996
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.1996.tb03149.x
Subject(s) - carcinogen , 2 acetylaminofluorene , quinoxaline , medicine , endocrinology , chemistry , glutathione , carcinogenesis , anticarcinogen , dose–response relationship , heterocyclic amine , biochemistry , biology , cancer , enzyme , microsome , organic chemistry
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 6 weeks, and partially hepatectomized 1 week after the beginning of MeIQx administration. Quantitative values for glutathione S‐transferase placental form (GST‐P)‐positiye 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.