Identification of Aflatoxin M1-N7-Guanine in Liver and Urine of Tree Shrews and Rats Following Administration of Aflatoxin B1
| Autor: | Jesse K. Johnson, Thomas W. Kensler, Bill D. Roebuck, Patricia A. Egner, Christopher K. Nathasingh, John D. Groopman, Xiang Yu |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Male
Aflatoxin Aflatoxin B1 Guanine Administration Oral Urine Biology Hydroxylation Toxicology Mass Spectrometry DNA Adducts chemistry.chemical_compound medicine Animals Bioassay Creatinine Tupaiidae General Medicine Metabolism medicine.disease Molecular biology Rats Inbred F344 Rats Liver Biochemistry chemistry Models Animal Aflatoxin M1 Microsomes Liver Liver cancer DNA Chromatography Liquid DNA Damage |
| Zdroj: | Chemical Research in Toxicology. 16:1174-1180 |
| ISSN: | 1520-5010 0893-228X |
| Popis: | Epidemiological studies have shown that exposure to aflatoxin B(1) (AFB(1)) 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 AFB(1) 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)-N(7)-guanine (AFM(1)-N(7)-guanine), was detected in urine and hepatic DNA samples 24 h after administration of 400 microg/kg AFB(1). In hepatic DNA isolated from tree shrews, AFM(1)-N(7)-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)-N(7)-guanine. Conversely, in rat liver, 6.56 +/- 2.41 pmol/mg DNA of AFB(1)-N(7)-guanine and 0.42 +/- 0.13 pmol/mg DNA of AFM(1)-N(7)-guanine were detected. Rats excreted 1.00 +/- 0.21 pmol AFB(1)-N(7)-guanine/mg creatinine and 0.29 +/- 0.10 pmol AFM(1)-N(7)-guanine/mg creatinine as compared to 0.60 +/- 0.12 pmol AFB(1)-N(7)-guanine/mg creatinine and 0.69 +/- 0.16 pmol AFM(1)-N(7)-guanine/mg creatinine excreted by the tree shrew. Furthermore, tree shrew urine contained 40 times more of the hydroxylated metabolite, AFM(1), than was excreted by rats. In vitro experiments confirmed this difference in oxidative metabolism. Hepatic microsomes isolated from tree shrews failed to produce aflatoxin Q(1) or aflatoxin P(1) but formed a significantly greater amount of AFM(1) than rat microsomes. Bioassays indicated that the tree shrew was considerably more resistant than the rat to AFB(1) hepatocarcinogenesis, which may reflect the significant differences in metabolic profiles of the two species. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|