Identification of aflatoxin M1-N7-guanine in liver and urine of tree shrews and rats following administration of aflatoxin B 1

Patricia A. Egner, Xiang Yu, Jesse K. Johnson, Christopher K. Nathasingh, John D. Groopman, Thomas W. Kensler, Bill D. Roebuck

Research output: Contribution to journalArticle

Abstract

Epidemiological studies have shown that exposure to aflatoxin B 1 (AFB1) and concurrent infection with hepatitis B lead to a multiplicative risk of developing liver cancer. This chemical-viral interaction can be recapitulated in the tree shrew (Tupia belangeri chinensis). As an initial characterization of this model, the metabolism of AFB1 in tree shrews has been examined and compared to a sensitive bioassay species, the rat. Utilizing LC/MS/MS, an unreported product, aflatoxin M 1-N7-guanine (AFM1-N7-guanine), was detected in urine and hepatic DNA samples 24 h after administration of 400 μg/kg AFB1. In hepatic DNA isolated from tree shrews, AFM -N7-guanine was the predominant adduct, 0.74 ± 0. 14 pmol/mg DNA, as compared to 0.37 ± 0.07 pmol/mg DNA of AFB 1-N7-guanine. Conversely, in rat liver, 6.56 ± 2. 41 pmol/mg DNA of AFB1,-N7-guanine and 0.42 ± 0.13 pmol/mg DNA of AFM1-N7-guanine were detected. Rats excreted 1.00 ± 0.21 pmol AFB1-N7-guanine/mg creatinine and 0.29 ± 0.10 pmol AFM1-N7-guanine/mg creatinine as compared to 0.60 ± 0.12 pmol AFB1-N 7-guanine/mg creatinine and 0.69 ± 0.16 pmol AFM 1-N7-guanine/mg creatinine excreted by the tree shrew. Furthermore, tree shrew urine contained 40 times more of the hydroxylated metabolite, AFM1, than was excreted by rats. In vitro experiments confirmed this difference in oxidative metabolism. Hepatic microsomes isolated from tree shrews failed to produce aflatoxin Q1 or aflatoxin P 1 but formed a significantly greater amount of AFM1 than rat microsomes. Bioassays indicated that the tree shrew was considerably more resistant than the rat to AFB1 hepatocarcinogenesis, which may reflect the significant differences in metabolic profiles of the two species.

Original languageEnglish (US)
Pages (from-to)1174-1180
Number of pages7
JournalChemical research in toxicology
Volume16
Issue number9
DOIs
StatePublished - Sep 1 2003

ASJC Scopus subject areas

  • Toxicology

Fingerprint Dive into the research topics of 'Identification of aflatoxin M<sub>1</sub>-N<sup>7</sup>-guanine in liver and urine of tree shrews and rats following administration of aflatoxin B <sub>1</sub>'. Together they form a unique fingerprint.

  • Cite this