Modulation of aflatoxin B1 biotransformation in rabbit pulmonary and hepatic microsomes

Daniels, Jonathan M.; Massey, Thomas E.

doi:10.1016/0300-483x(92)90040-l

Cited by 20 publications

(10 citation statements)

References 35 publications

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“…The induction profile of AFB1 metabolites by BNF was similar to that obtained from BNF-treated mice (Raina et al 1985;Koser et al 1988) and rabbits (Daniels and Massey 1992). The data indicate that, unlike the P450 isozyme(s) catalyzing the epoxidation of AFB], BNF-inducible P450 isozymes of the P4501A class are responsible for the biotransformation of AFB1 to the less reactive metabolite, AFM 1.…”

Section: Discussionsupporting

confidence: 75%

“…For example, BNF treatment reduced AFB1-DNA binding and hepatocarcinogenesis in rats (Lotlikar 1989) and rainbow trout (Goeger et al 1988), and depressed mouse liver microsome-mediated AFB1 mutagenicity (Raina et al 1985). In addition, the pulmonary and hepatic production of AFMI, a non-toxic metabolite of AFB1, has been found to be induced by BNF treatment in mice (Raina et al 1985;Koser et al 1988) and rabbits (Daniels and Massey 1992). Therefore, BNF-treatment is generally considered to enhance detoxification of AFB t. However, experiments with hamsters have demonstrated that an AFBt-activating P450 isozyme can be greatly induced by BNF (Santhanam and Lotlikar 1989), suggesting the presence of species heterogeneity in the modification of AFB1 metabolism by PAH-type inducers.…”

Section: Introductionmentioning

confidence: 95%

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In vitro cytochrome P450 monooxygenase and prostaglandin H-synthase mediated aflatoxin B1 biotransformation in guinea pig tissues: Effects of β-naphthoflavone treatment

1993

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In the present study, we examined the effects of treating guinea pigs with beta-naphthoflavone (BNF) on aflatoxin B1 (AFB1) metabolism by microsomal cytochrome P450 monooxygenase (P450) and prostaglandin H synthase (PHS) in liver, lung and kidney tissues. After BNF treatment, microsomal 7-ethoxyresorufin O-deethylase activity was induced 13-, 25- and 11-fold in lung, kidney and liver, respectively, confirming that the BNF treatment protocol was effective at inducing monooxygenase activity. Treatment of guinea pigs with BNF did not change [3H]AFB1-DNA binding catalyzed by microsomal PHS or P450 in lung, kidney or liver. In contrast, AFM1 formation by P450 was significantly increased in microsomes from all three organs. The data indicate that BNF-inducible P450 isozymes of the P4501A class are responsible for the biotransformation of AFB1 to non-toxic metabolites. Guinea pig kidney microsomes could also catalyze NADPH-dependent formation of aflatoxicol (AFL), a metabolite usually produced by a cytosolic steroid dehydrogenase. Renal microsomal AFL formation was not altered by prior BNF treatment. The results in the present study suggest that BNF may alter the bioactivation of AFB1 in guinea pig tissues by inducing P450 activity, leading to the formation of less reactive metabolite.

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Section: Discussionsupporting

confidence: 75%

Section: Introductionmentioning

confidence: 95%

In vitro cytochrome P450 monooxygenase and prostaglandin H-synthase mediated aflatoxin B1 biotransformation in guinea pig tissues: Effects of β-naphthoflavone treatment

1993

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“…They identified Yc 2 subunit of GST, which had high catalytic activity toward AFB 1 . Daniels and Massey (1992) investigated the role of polycyclic aromatic hydrocarbon-inducible forms of cytochrome-P 450 in the pulmonary and hepatic microsomal activation ( 3 [H] AFB 1 -DNA binding) and detoxification ( 3 [H] AFM 1 and 3 [H] AFQ 1 formation) of 3 [H] AFB 1 . They determined K m and V max of each reaction using different combinations of alpha and beta napthoflavone and in the presence or absence of NADPH-generating systems.…”

Section: B Nuclear Metabolismmentioning

confidence: 99%

A Review on Biological Control and Metabolism of Aflatoxin

Mishra¹,

Das²

2003

Critical Reviews in Food Science and Nutrition

251

135

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The series of events that led to the discovery of aflatoxin as a potent carcinogen, its biosynthesis, mechanism of action, structure-function relationship provide interesting insight into the economical and technological factors involved in the development of an effective control measure for the toxin. Scientists all over the world are making continuous efforts to explore a generalized process of detoxification, which can bring down the toxin content in heterogenous commodities to a threshold level. In this article biological control methods with special emphasis on in vivo and in vitro enzymatic detoxification of aflatoxin have been reviewed. Future areas of research involving large-scale enzymatic detoxification and modified atmosphere storage are also discussed.

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“…Human exposure occurs either by ingestion or inhalation of AFB 1 contaminated agricultural products [1]. In order to exert its biological effects, AFB 1 must be converted into its reactive epoxide, which is catalysed by the cytochrome P450-dependent mixed function oxygenase (MFO) system in liver [2] and extrahepatic tissues like lung [3].…”

Section: Introductionmentioning

confidence: 99%

“…The genotoxic effects of AFB 1 can be assessed by various methods, amongst which the micronucleus test is preferred for its ease and accuracy [5]. Micronuclei are cytoplasmic chromatin masses with the appearance of small nuclei that arise from broken chromosomal fragments under the action of clastogenic chemicals like AFB 1 . The micronucleus test is carried out on rapidly proliferating cells, most commonly the bone marrow cells.…”

Section: Introductionmentioning

confidence: 99%

Aflatoxin B1-induced micronuclei and cell cycle alterations in lung and bone marrow cells and their modulation byPiper argyrophyllumextract

Raj¹,

Gupta²,

Rohil³

et al. 1998

Teratog. Carcinog. Mutagen.

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Modulation of aflatoxin B1 biotransformation in rabbit pulmonary and hepatic microsomes

Cited by 20 publications

References 35 publications

In vitro cytochrome P450 monooxygenase and prostaglandin H-synthase mediated aflatoxin B1 biotransformation in guinea pig tissues: Effects of β-naphthoflavone treatment

In vitro cytochrome P450 monooxygenase and prostaglandin H-synthase mediated aflatoxin B1 biotransformation in guinea pig tissues: Effects of β-naphthoflavone treatment

A Review on Biological Control and Metabolism of Aflatoxin

Aflatoxin B1-induced micronuclei and cell cycle alterations in lung and bone marrow cells and their modulation byPiper argyrophyllumextract

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