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Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1990 May;81(5):470–476. doi: 10.1111/j.1349-7006.1990.tb02593.x

DNA Adducts Formed by 2‐Amino‐3,8‐dimethylimidazo[4,5‐f]quinoxaline in Rat Liver: Dose‐Response on Chronic Administration

Katsumi Yamashita 1,†, Masaaki Adachi 1, Shunji Kato 1, Hitoshi Nakagama 2, Masako Ochiai 2, Keiji Wakabayashi 2, Shigeaki Sato 1,‡, Minako Nagao 2,✉, Takashi Sugimura 1,2
PMCID: PMC5918071  PMID: 2116395

Abstract

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 32P‐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 107 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 107 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.

Keywords: DNA adducts, 32P‐Postlabeling analysis, MeIQx, mdr gene

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