Open AccessFormation and Removal of DNA Adducts in the Liver of Rats Chronically Fed the Food‐borne Carcinogen, 2‐Amino‐3,8‐dimethylimidazo[4,5‐ f ]quinoxaline
Author(s) -
Hirose Misako,
Wakabayashi Keiji,
Ochiai Masako,
Kushida Hiromi,
Sato Hidetaka,
Sugimura Takashi,
Nagao Minako
Publication year - 1995
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.1349-7006.1995.tb02428.x
Subject(s) - carcinogen , chemistry , adduct , quinoxaline , dna adduct , dna , heterocyclic amine , heterocyclic compound , 2 acetylaminofluorene , medicine , endocrinology , biochemistry , enzyme , biology , organic chemistry , microsome
Effects of chronic administration of 2‐amino‐3,8‐dimethylimidazo[4,5‐ f ]quinoxaline (MeIQx) at 0.4, 8 and 400 ppm in the diet on DNA adduct formation and removal in the rat liver were examined by the 32 P‐postlabeling method. The 0.4 and 8 ppm doses for 40 weeks resulted in time‐dependent increases in MeIQx‐DNA adduct levels until 16 and 8 weeks, respectively, with constant values being maintained thereafter. In the case of a carcinogenic dose (400 ppm) of MeIQx, the adduct levels reached a maximum at week 12, and then gradually decreased. Alteration of metabolism of MeIQx during liver carcinogenesis might be related to this decrease in DNA adduct levels. When MeIQx administration was stopped at week 20, 60–90% of the MeIQx‐DNA adducts formed with the three doses (0.4, 8 and 400 ppm) of MeIQx were removed in a biphasic manner after return to a basal diet, with initial rapid removal followed by a slow change. No difference in the pattern of MeIQx‐DNA adducts was detected on thin layer chromatography at any dose at any time point. Thus, it is suggested that there may be at least two types of damaged DNA, susceptible and resistant to removal of MeIQx‐DNA adducts, after chronic administration of MeIQx.