Covalent binding of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline to albumin and hemoglobin at environmentally relevant doses

Comparison of human subjects and f344 rats

Karen H. Dingley, Stewart P H T Freeman, David O. Nelson, R. Colin Garner, Ken W Turteltaub

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Covalent binding of the food-bome heterocyclic amine 2-amino-3,8- dimethylimidazo[4,5-f]quinoxaline (MelQx) to albumin and hemoglobin (Hb), 3.5-6.0 hr after oral administration of a single dose of either 21.3 or 228.0 μg of [14C]MelQx (304 and 3257 ng/kg of body weight, respectively, based on a 70-kg subject weight), was studied in human volunteers using accelerator mass spectrometry. Human protein adduct levels were compared with data obtained for male F344 rats 4.5 hr after oral administration of 0.94-11,420 ng/kg of body weight [14C]MelQx. Dose-dependent levels of MelQx-albumin and MelQx-Hb adducts were detected in both humans and rats. In each case, the regression coefficient (slope) of the dose-response curve was approximately 1. The highest levels of adduct formation per unit dose of MelQx occurred with human albumin, followed by rat albumin, human Hb, and rat Hb (in that order). Although the human subjects were elderly and underwent colon resection surgery during the study period, the results indicate that formation of albumin and Hb adducts is dose dependent and that a trend exists for higher adduct levels per unit dose in humans, compared with F344 rats. Furthermore, MelQx-albumin adducts are likely to provide a more sensitive marker of exposure to MelQx than are MelQx-Hb adducts.

Original languageEnglish (US)
Pages (from-to)825-828
Number of pages4
JournalDrug Metabolism and Disposition
Volume26
Issue number8
StatePublished - Aug 1998
Externally publishedYes

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2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline
Inbred F344 Rats
Rats
Albumins
Hemoglobins
Oral Administration
Body Weight
Surgery
Particle accelerators
Amines
Mass spectrometry
Volunteers

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

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Covalent binding of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline to albumin and hemoglobin at environmentally relevant doses : Comparison of human subjects and f344 rats. / Dingley, Karen H.; Freeman, Stewart P H T; Nelson, David O.; Garner, R. Colin; Turteltaub, Ken W.

In: Drug Metabolism and Disposition, Vol. 26, No. 8, 08.1998, p. 825-828.

Research output: Contribution to journalArticle

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abstract = "Covalent binding of the food-bome heterocyclic amine 2-amino-3,8- dimethylimidazo[4,5-f]quinoxaline (MelQx) to albumin and hemoglobin (Hb), 3.5-6.0 hr after oral administration of a single dose of either 21.3 or 228.0 μg of [14C]MelQx (304 and 3257 ng/kg of body weight, respectively, based on a 70-kg subject weight), was studied in human volunteers using accelerator mass spectrometry. Human protein adduct levels were compared with data obtained for male F344 rats 4.5 hr after oral administration of 0.94-11,420 ng/kg of body weight [14C]MelQx. Dose-dependent levels of MelQx-albumin and MelQx-Hb adducts were detected in both humans and rats. In each case, the regression coefficient (slope) of the dose-response curve was approximately 1. The highest levels of adduct formation per unit dose of MelQx occurred with human albumin, followed by rat albumin, human Hb, and rat Hb (in that order). Although the human subjects were elderly and underwent colon resection surgery during the study period, the results indicate that formation of albumin and Hb adducts is dose dependent and that a trend exists for higher adduct levels per unit dose in humans, compared with F344 rats. Furthermore, MelQx-albumin adducts are likely to provide a more sensitive marker of exposure to MelQx than are MelQx-Hb adducts.",
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