Comparison of DNA-adduct and tissue-available dose levels of MeIQx in human and rodent colon following administration of a very low dose

Robert J. Mauthe, Karen H. Dingley, Steven H. Leveson, Stewart P H T Freeman, Robert J. Turesky, R. Colin Garner, Ken W Turteltaub

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Abstract

[2-14C]2-amino-3,8-dimethylimidazo [4,5-f]quinoxaline (MeIQx) was administered orally (304 ng/kg body-weight dose based upon an average 70-kg- body-weight subject) to 5 human colon-cancer patients (58 to 84 years old), as well as to F344 rats and B6C3F1 mice. Colon tissue was collected from the human subjects at surgery and from the rodents 3.5 to 6 hr after administration. Colon DNA-adduct levels and tissue available doses were measured by accelerator mass spectrometry (AMS). The mean levels of MeIQx in the histologically normal colon tissue were not different among the human (97 ± 26 pg MeIQx/g), rat (133 ± 15 pg/g) or mouse (78 ± 10 pg/g) tissues; and no difference existed between the levels detected in human normal and tumor tissue (101 ± 15 pg/g). Mean DNA-adduct levels in normal human colon (26 ± 4 adducts/1012 nucleotides) were significantly greater (p < 0.01) than in rats (17.1 ± 1 adduct/1012 nucleotides) or mice (20.6 ± 0.9 adduct/1012 nucleotides). No difference existed in adduct levels between normal and tumor tissue in humans. These results show that MeIQx forms DNA adducts in human colon at low dose, and that the human colon may be more sensitive to the effects of MeIQx than that of mice or rats.

Original languageEnglish (US)
Pages (from-to)539-545
Number of pages7
JournalInternational Journal of Cancer
Volume80
Issue number4
DOIs
StatePublished - Feb 4 1999
Externally publishedYes

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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