Open AccessDNA Adducts Formed by 2‐Amino‐3,8‐dimethylimidazo[4,5‐ f ]quinoxaline in Rat Liver: Dose‐Response on Chronic Administration
Author(s) -
Yamashita Katsumi,
Adachi Masaaki,
Kato Shunji,
Nakagama Hitoshi,
Ochiai Masako,
Wakabayashi Keiji,
Sato Shigeaki,
Nagao Minako,
Sugimura Takashi
Publication year - 1990
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.1349-7006.1990.tb02593.x
Subject(s) - quinoxaline , adduct , dna , pharmacology , chemistry , biology , biochemistry , genetics , medicine , organic chemistry
The effect of administration of 2‐amino‐3,8‐dimethylimidazo[4,5‐ f ]quinoxaline (MeIQx) at various doses on DNA adduct formation in male rats was examined by 32 P‐postlabeling analysis. Administration of MeIQx in the diet at 0.4 ppm, 4 ppm, 40 ppm and 400 ppm for one week resulted in the formations of 0.04, 0.28, 3.34 and 39.0 adducts per 10 7 nucleotides in rat liver cells. Continuous administration of 400 ppm of MeIQx in the diet for 61 weeks to rats induced hepatocellular carcinomas in all rats. The carcinogenicity of MeIQx at doses of 40 ppm or less is not known yet, but the above results show a linear relationship between the level of MeIQx administered and the adduct level. In rats treated with low doses of 0.4, 4 and 40 ppm of MeIQx, adduct levels increased linearly with time of treatment, the levels in week 12 being two to three times those in week 1. In contrast, on treatment with 400 ppm of MeIQx, the adduct level in the liver increased until week 4, when it was 110 adducts per 10 7 nucleotides, and then remained constant for the next 8 weeks. Induction of the multidrug‐resistance gene was suggested to be involved in development of this plateau level.