Activation and detoxication of aflatoxin B1

Fp, Guengerich; Ww, Johnson; Shimada, Tsutomu; Yf, Ueng; Yamazaki, Hiroshi; Langouët, Sophie

doi:10.1016/s0027-5107(97)00289-3

Cited by 282 publications

(184 citation statements)

References 42 publications

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“…This result is consistent with the findings of Guengerich et al (1998), who reported that highly reactive AFB 1 -exo-8,9-epoxide is able to form adducts with DNA that are directly proportional to AFB 1 dose (Choy, 1993). DNA release may either stimulate or inhibit immune cell activation, depending on its concentration, sequence, and context (Scaffidi et al, 2002).…”

Section: Discussionsupporting

confidence: 92%

In-vitro cytotoxicity of aflatoxin B1 to broiler lymphocytes of broiler chickens

Zimmermann

Machado

Cadoná

et al. 2014

Rev. Bras. Cienc. Avic.

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The aim of the present work was to study the in-vitro cytotoxic effects of different concentrations of aflatoxin B 1 (AFB 1 ) on broiler lymphocytes. Lymphocyte-rich mononuclear cells were separated by Ficoll-Histopaque density and cultured in 96-wellplates containing the evaluated AFB 1 concentrations in 5% CO 2 atmosphere at 39°C. Thereafter, MTT, PicoGreen, and reactive oxygen species assays were performed. Cell viability decreased in the presence of 10 µg/mL AFB 1 at 48 h (p < 0.05) and of 10 and 20 µg/mL AFB 1 at 72 h (p < 0.01 and p < 0.001, respectively) when compared to the control (0 µg/mL). However, a dose-dependent increase in the cell-free DNA at 24 h was observed at 1, 10 and 20 µg/mL (p < 0.001). ROS formation significantly increased at 24 h at all concentrations (p < 0.001). The in-vitro results demonstrate that AFB 1 is cytotoxic and causes biomolecular oxidative damage in broiler lymphocytes.

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Section: Discussionsupporting

confidence: 92%

In-vitro cytotoxicity of aflatoxin B1 to broiler lymphocytes of broiler chickens

Zimmermann

Machado

Cadoná

et al. 2014

Rev. Bras. Cienc. Avic.

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“…Therefore, AFB1 has been classified as a category I known human carcinogen by the International Agency for Research on Cancer (24). AFB1 is metabolized by cytochrome P450 enzymes to its reactive form, AFB1-8,9-epoxide (AFB1-epoxide), which covalently binds to DNA and induces DNA damage (19,(25)(26)(27)(28). DNA damage induced by AFB1 includes AFB1-DNA adducts, oxidative DNA damage, www.intechopen.com and gene mutation (Fig.…”

Section: Afb1 Exposure and Dna Damage And Repairmentioning

confidence: 99%

DNA Repair Capacity-Related to Genetic Polymorphisms of DNA Repair Genes and Aflatoxin B1-Related Hepatocellular Carcinoma Among Chinese Population

Long¹,

Yao²,

Zeng³

et al. 2011

DNA Repair

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“…2,[14][15][16] However, quantitative data on AFM 1 excretion into feces are limited. 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%

“…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.…”

mentioning

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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Activation and detoxication of aflatoxin B1

Cited by 282 publications

References 42 publications

In-vitro cytotoxicity of aflatoxin B1 to broiler lymphocytes of broiler chickens

In-vitro cytotoxicity of aflatoxin B1 to broiler lymphocytes of broiler chickens

DNA Repair Capacity-Related to Genetic Polymorphisms of DNA Repair Genes and Aflatoxin B1-Related Hepatocellular Carcinoma Among Chinese Population

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

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Activation and detoxication of aflatoxin B1

Cited by 282 publications

References 42 publications

In-vitro cytotoxicity of aflatoxin B1 to broiler lymphocytes of broiler chickens

In-vitro cytotoxicity of aflatoxin B1 to broiler lymphocytes of broiler chickens

DNA Repair Capacity-Related to Genetic Polymorphisms of DNA Repair Genes and Aflatoxin B1-Related Hepatocellular Carcinoma Among Chinese Population

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

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