Aflatoxin b1 hydroxylation by the pregnenolone-16α-carbonitrile-inducible form of rat liver microsomal cytochrome p-450

Michael R. Halvorson; Steven H. Safe; Andrew Parkinson; Timothy D. Phillips

doi:10.1093/carcin/9.11.2103

Aflatoxin b₁ hydroxylation by the pregnenolone-16α-carbonitrile-inducible form of rat liver microsomal cytochrome p-450

Michael R. Halvorson, Steven H. Safe, Andrew Parkinson, Timothy D. Phillips

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Abstract

The effects of treating rats with various pregnenolone-16α-carbonitrile (PCN)-type inducers of cytochrome P-450p on the liver microsomal metabolism of aflatoxin B₁ (AFB₁) were investigated. Treatment of male rats with PCN resulted in a 6-fold increase in the 9-hydroxylation of AFB₁ to aflatoxin Q₁ (AFQ₁). Treatment of female rats with PCN resulted in a 16-fold increase in the formation of AFQ₁. The age-dependent decline in constitutive cytochrome P-450p levels in female but not male rats resulted in a sex difference in the formation of AFQ₁ in liver microsomes from untreated rats (male: female ∼ 3: 1). The formation of AFQ₁ was stimulated up to 5.4-fold when liver microsomes from triacetyloleandomycin (TAO)-treated rats were treated with potassium ferricyanide, which dissociates the complex between cytochrome P-450p and TAO. Treatment of male rats with the cytochrome P-450p inducer, dexamethasone, increased (∼ 7-fold) the 9-hydroxylation of AFB₁ to AFQ₁ by liver microsomes, and also enhanced (∼ 2-fold) the microsomal activation of AFB₁ to metabolites that were mutagenic to Salmonella typhimurium TA98 and TA100. These results indicate that the 9-hydroxylation of AFB₁ to AFQ₁ is catalyzed by rat liver microsomal cytochrome P-450p.

Original language	English (US)
Pages (from-to)	2103-2108
Number of pages	6
Journal	Carcinogenesis
Volume	9
Issue number	11
DOIs	https://doi.org/10.1093/carcin/9.11.2103
State	Published - Nov 1988

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Cancer Research

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10.1093/carcin/9.11.2103

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@article{6f87d01fa9b246329dde223e9654c244,

title = "Aflatoxin b1 hydroxylation by the pregnenolone-16α-carbonitrile-inducible form of rat liver microsomal cytochrome p-450",

abstract = "The effects of treating rats with various pregnenolone-16α-carbonitrile (PCN)-type inducers of cytochrome P-450p on the liver microsomal metabolism of aflatoxin B1 (AFB1) were investigated. Treatment of male rats with PCN resulted in a 6-fold increase in the 9-hydroxylation of AFB1 to aflatoxin Q1 (AFQ1). Treatment of female rats with PCN resulted in a 16-fold increase in the formation of AFQ1. The age-dependent decline in constitutive cytochrome P-450p levels in female but not male rats resulted in a sex difference in the formation of AFQ1 in liver microsomes from untreated rats (male: female ∼ 3: 1). The formation of AFQ1 was stimulated up to 5.4-fold when liver microsomes from triacetyloleandomycin (TAO)-treated rats were treated with potassium ferricyanide, which dissociates the complex between cytochrome P-450p and TAO. Treatment of male rats with the cytochrome P-450p inducer, dexamethasone, increased (∼ 7-fold) the 9-hydroxylation of AFB1 to AFQ1 by liver microsomes, and also enhanced (∼ 2-fold) the microsomal activation of AFB1 to metabolites that were mutagenic to Salmonella typhimurium TA98 and TA100. These results indicate that the 9-hydroxylation of AFB1 to AFQ1 is catalyzed by rat liver microsomal cytochrome P-450p.",

author = "Halvorson, {Michael R.} and Safe, {Steven H.} and Andrew Parkinson and Phillips, {Timothy D.}",

note = "Funding Information: This work was supported by USDA Project 84-CRSR-2-2434 and USAID CRSP Project 02-50305-2. A.P. is a recipient of a Research Career Development Award from NIH (ES 00166) and is supported by NIH grants ES 03765 and GM 37044. Copyright: Copyright 2010 Elsevier B.V., All rights reserved.",

year = "1988",

month = nov,

doi = "10.1093/carcin/9.11.2103",

language = "English (US)",

volume = "9",

pages = "2103--2108",

journal = "Carcinogenesis",

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publisher = "Oxford University Press",

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T1 - Aflatoxin b1 hydroxylation by the pregnenolone-16α-carbonitrile-inducible form of rat liver microsomal cytochrome p-450

AU - Halvorson, Michael R.

AU - Safe, Steven H.

AU - Parkinson, Andrew

AU - Phillips, Timothy D.

N1 - Funding Information: This work was supported by USDA Project 84-CRSR-2-2434 and USAID CRSP Project 02-50305-2. A.P. is a recipient of a Research Career Development Award from NIH (ES 00166) and is supported by NIH grants ES 03765 and GM 37044. Copyright: Copyright 2010 Elsevier B.V., All rights reserved.

PY - 1988/11

Y1 - 1988/11

N2 - The effects of treating rats with various pregnenolone-16α-carbonitrile (PCN)-type inducers of cytochrome P-450p on the liver microsomal metabolism of aflatoxin B1 (AFB1) were investigated. Treatment of male rats with PCN resulted in a 6-fold increase in the 9-hydroxylation of AFB1 to aflatoxin Q1 (AFQ1). Treatment of female rats with PCN resulted in a 16-fold increase in the formation of AFQ1. The age-dependent decline in constitutive cytochrome P-450p levels in female but not male rats resulted in a sex difference in the formation of AFQ1 in liver microsomes from untreated rats (male: female ∼ 3: 1). The formation of AFQ1 was stimulated up to 5.4-fold when liver microsomes from triacetyloleandomycin (TAO)-treated rats were treated with potassium ferricyanide, which dissociates the complex between cytochrome P-450p and TAO. Treatment of male rats with the cytochrome P-450p inducer, dexamethasone, increased (∼ 7-fold) the 9-hydroxylation of AFB1 to AFQ1 by liver microsomes, and also enhanced (∼ 2-fold) the microsomal activation of AFB1 to metabolites that were mutagenic to Salmonella typhimurium TA98 and TA100. These results indicate that the 9-hydroxylation of AFB1 to AFQ1 is catalyzed by rat liver microsomal cytochrome P-450p.

AB - The effects of treating rats with various pregnenolone-16α-carbonitrile (PCN)-type inducers of cytochrome P-450p on the liver microsomal metabolism of aflatoxin B1 (AFB1) were investigated. Treatment of male rats with PCN resulted in a 6-fold increase in the 9-hydroxylation of AFB1 to aflatoxin Q1 (AFQ1). Treatment of female rats with PCN resulted in a 16-fold increase in the formation of AFQ1. The age-dependent decline in constitutive cytochrome P-450p levels in female but not male rats resulted in a sex difference in the formation of AFQ1 in liver microsomes from untreated rats (male: female ∼ 3: 1). The formation of AFQ1 was stimulated up to 5.4-fold when liver microsomes from triacetyloleandomycin (TAO)-treated rats were treated with potassium ferricyanide, which dissociates the complex between cytochrome P-450p and TAO. Treatment of male rats with the cytochrome P-450p inducer, dexamethasone, increased (∼ 7-fold) the 9-hydroxylation of AFB1 to AFQ1 by liver microsomes, and also enhanced (∼ 2-fold) the microsomal activation of AFB1 to metabolites that were mutagenic to Salmonella typhimurium TA98 and TA100. These results indicate that the 9-hydroxylation of AFB1 to AFQ1 is catalyzed by rat liver microsomal cytochrome P-450p.

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JO - Carcinogenesis

JF - Carcinogenesis

SN - 0143-3334

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ER -

Aflatoxin b₁ hydroxylation by the pregnenolone-16α-carbonitrile-inducible form of rat liver microsomal cytochrome p-450

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