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Comparison of DNA‐adduct and tissue‐available dose levels of MeIQx in human and rodent colon following administration of a very low dose
Author(s) -
Mauthe Robert J.,
Dingley Karen H.,
Leveson Steven H.,
Freeman Stewart P.H.T.,
Turesky Robert J.,
Garner R. Colin,
Turteltaub Kenneth W.
Publication year - 1999
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19990209)80:4<539::aid-ijc10>3.0.co;2-c
Subject(s) - dna adduct , adduct , nucleotide , medicine , colorectal cancer , endocrinology , chemistry , carcinogen , cancer , biochemistry , biology , gene , organic chemistry
[2‐ 14 C]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 B 6 C 3 F 1 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/10 12 nucleotides) were significantly greater ( p < 0.01) than in rats (17.1 ± 1 adduct/10 12 nucleotides) or mice (20.6 ± 0.9 adduct/10 12 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. Int. J. Cancer 80:539–545, 1999. © 1999 Wiley‐Liss, Inc.