Metabolism and Toxicity of Aflatoxins M1and B1in Human-Derivedin VitroSystems

Neal, G.E.; Eaton, David L.; Judah, David J.; Verma, Ankur

doi:10.1006/taap.1998.8440

Cited by 130 publications

(95 citation statements)

References 15 publications

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“…On the the hand, very sensitive detection systems such as fluorescence detection and enzyme-linked immunosorbent assay (ELISA) as used in the studies of Polychronaki et al (2008) andGong et al (2003) allowed detection at very low picogram/mL levels and hence possibly led to an increase in the power of their statistical prediction. It is worth noting that despite being a weaker carcinogen, AFM1 is as cytotoxic as AFB1 (Neal et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Multimycotoxin analysis in urines to assess infant exposure: A case study in Cameroon

Ediage

Mavungu

Song

et al. 2013

Environment International

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Section: Discussionmentioning

confidence: 99%

Multimycotoxin analysis in urines to assess infant exposure: A case study in Cameroon

Ediage

Mavungu

Song

et al. 2013

Environment International

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“…On the other hand, CYP3A4 is known as one of the major CYP enzymes in the liver, 13,[17][18][19][20] and in vitro studies using primate and human liver microsomes have demonstrated that AFQ 1 is a major AFB 1 metabolite. 21,22 Excretion of AFQ 1 , especially fecal excretion in humans, has not been quantitatively or qualitatively characterized.…”

Section: Guanine; Hepatitis B Virusmentioning

confidence: 99%

Fecal and urinary excretion of aflatoxin B₁ metabolites (AFQ₁, AFM₁ and AFB‐N⁷‐guanine) in young Chinese males

Mykkänen

Zhu

Salminen

et al. 2005

Intl Journal of Cancer

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Our study was designed to assess the fecal and urinary excretion of 3 aflatoxin B 1 (AFB 1 ) metabolites, aflatoxins M 1 (AFM 1 ) and Q 1 (AFQ 1 ) and aflatoxin B 1 -N 7 -guanine (AFB-N 7 -guanine) that are produced by the predominant forms of cytochrome P450 enzymes responsible for the biotransformation of AFB 1 . Fecal and urinary AFM 1 , AFQ 1 and urinary AFB-N 7 -guanine were assessed in 83 young Chinese males selected from a larger population (n = 300) based on detectable urinary AFM 1 . The concentration of fecal AFQ 1 (median 137 ng/g fresh weight, IQR 9.1 to 450) was approximately 60 times higher than that of AFM 1 (2.3 ng/g, IQR 0.0 to 7.3). In urine, the median AFQ 1 was 10.4 ng/ml (IQR 3.4 to 23.3), and the median AFM 1 and AFB-N 7 -guanine 0.04 ng/ml (IQR 0.01 to 0.33) and 0.38 ng/ml (IQR 0.0 to 2.15), respectively. A subgroup (n = 14) with hepatitis B virus (HBV) infection had significantly higher fecal concentrations of AFQ 1 ( p = 0.043) and AFM 1 ( p = 0.001) than those who were hepatitis B-virus antigen (HBsAg) negative, and the respective differences in urinary AFQ 1 and AFM 1 concentrations approached statistical significance ( p = 0.054, p = 0.138). Our study demonstrates that AFQ 1 is excreted in urine and feces at higher levels than AFM 1 , and feces are an important route of excretion of these AFB 1 metabolites. AFQ 1 should be further assessed for its predictive value as a marker for exposure and risk of dietary aflatoxins. The most serious health effect of dietary exposure to aflatoxins is hepatocellular carcinoma. The etiology of this disease also involves chronic infection with hepatitis B and C viruses (HBV and HCV), and a significant synergistic interaction between aflatoxin exposure and hepatitis B virus has been reported. 2,3After oral uptake AFB 1 is efficiently absorbed and metabolized prior to excretion by fecal and urinary routes (Fig. 1). Absorbed AFB 1 and its metabolites are excreted in urine, while elimination to feces is a route for both the unabsorbed AFB 1 and biliary excretion of metabolites formed from the absorbed toxin. Animal studies have shown that under normal conditions 50% of the orally administered dose of AFB 1 is quickly absorbed from the duodenal region of the small intestine 4 and enters the liver through the hepatic portal blood supply.5 AFB 1 is concentrated in the liver and to a lesser extent in kidney, 6 and it is also found in the mesenteric venous blood as free AFB 1 or its water-soluble metabolites.Members of the cytochrome P450 (CYP) enzyme family, CYP1A2, CYP3A4 and CYP2A6 have been shown to be responsible for the metabolism of the absorbed aflatoxins 7,8 (Fig. 1). These enzymes convert AFB 1 to its carcinogenic form, AFB-8,9-epoxide, which is covalently bound to DNA 9 and serum albumin, 10 forming aflatoxin B 1 -N 7 -guanine (AFB-N 7 -guanine) and lysine adducts, respectively. These enzymes also oxidize AFB 1 to various other derivatives, including aflatoxin M 1 (AFM 1 ), aflatoxin Q 1 (AFQ 1 ), aflatoxin P 1 as well as a reduced aflatoxin species...

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“…However, in vitro studies using primate and human liver microsomes have demonstrated that AFQ 1 is a major AFB 1 metabolite, with AFM 1, the hydroxylated metabolite constituting less than 10% of the total metabolized AFB 1 [22][23]. Accordingly, in a study carried out in China, the levels of urinary AFQ 1 were 60 fold higher than those of AFM 1 .…”

Section: Introductionmentioning

confidence: 99%

A direct assessment of mycotoxin biomarkers in human urine samples by liquid chromatography tandem mass spectrometry

Ediage

Mavungu

Song

et al. 2012

Analytica Chimica Acta

119

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Metabolism and Toxicity of Aflatoxins M1and B1in Human-Derivedin VitroSystems

Cited by 130 publications

References 15 publications

Multimycotoxin analysis in urines to assess infant exposure: A case study in Cameroon

Multimycotoxin analysis in urines to assess infant exposure: A case study in Cameroon

Fecal and urinary excretion of aflatoxin B₁ metabolites (AFQ₁, AFM₁ and AFB‐N⁷‐guanine) in young Chinese males

A direct assessment of mycotoxin biomarkers in human urine samples by liquid chromatography tandem mass spectrometry

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Metabolism and Toxicity of Aflatoxins M1and B1in Human-Derivedin VitroSystems

Cited by 130 publications

References 15 publications

Multimycotoxin analysis in urines to assess infant exposure: A case study in Cameroon

Multimycotoxin analysis in urines to assess infant exposure: A case study in Cameroon

Fecal and urinary excretion of aflatoxin B1 metabolites (AFQ1, AFM1 and AFB‐N7‐guanine) in young Chinese males

A direct assessment of mycotoxin biomarkers in human urine samples by liquid chromatography tandem mass spectrometry

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Fecal and urinary excretion of aflatoxin B₁ metabolites (AFQ₁, AFM₁ and AFB‐N⁷‐guanine) in young Chinese males