3-Methylcholanthrene elicits DNA adduct formation in the CYP1A1 promoter region and attenuates reporter gene expression in rat H4IIE cells.

3-Methylcholanthrene elicits DNA adduct formation in the CYP1A1 promoter region and attenuates reporter gene expression in rat H4IIE cells. Research Abstract Details 

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3-Methylcholanthrene elicits DNA adduct formation in the CYP1A1 promoter region and attenuates reporter gene expression in rat H4IIE cells. Abstract Text:

Bhagavatula Moorthy,Kathirvel Muthiah,Inayat S Fazili,Sudha R Kondraganti,Lihua Wang,Xanthi I Couroucli,Weiwu Jiang,

Cytochrome CYP1A (CYP1A) enzymes catalyze bioactivation of 3-methylcholanthrene (MC) to genotoxic metabolites. Here, we tested the hypothesis that CYP1A2 catalyzes formation of MC-DNA adducts that are preferentially formed in the promoter region of CYP1A1, resulting in modulation of CYP1A1 gene expression. MC bound covalently to plasmid DNA (50 micro g) containing human CYP1A1 promoter (pGL3-1A1), when incubated with wild-type (WT) liver microsomes (2 mg) and NAPPH 37 degrees C for 2h, giving rise to 9 adducts, as determined by (32)P-postlabeling. Eighty percent of adducts was located in the promoter region. Transient transfection of the adducted plasmids into rat hepatoma (H4IIE) cells for 16h, followed by MC (1 micro M) treatment for 24h inhibited reporter (luciferase) gene expression by 75%, compared to unadducted controls. Our results suggest that CYP1A2 plays a key role in sequence-specific MC-DNA adduct formation in the CYP1A1 promoter region, leading to attenuation of CYP1A1 gene expression.

3-Methylcholanthrene elicits DNA adduct formation in the CYP1A1 promoter region and attenuates reporter gene expression in rat H4IIE cells. Publishing Authors By Initials

B Moorthy,K Muthiah,IS Fazili,SR Kondraganti,L Wang,XI Couroucli,W Jiang,

For similar investigative techniques: genetic techniques: gene transfer techniques: transfection research abstracts see: investigative techniques: genetic techniques: gene transfer techniques: transfection research

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3-Methylcholanthrene elicits DNA adduct formation in the CYP1A1 promoter region and attenuates reporter gene expression in rat H4IIE cells. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Biochemical and biophysical research communication

VOLUME: 354

Page Numbers: 1071-7

Journal Abbreviation: Biochem. Biophys. Res. Commun.

ISSN: 0006-291X

DAY: 26

MONTH: 01

YEAR: 2007

3-Methylcholanthrene elicits DNA adduct formation in the CYP1A1 promoter region and attenuates reporter gene expression in rat H4IIE cells. Information

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LANGUAGE: eng

NlmUniqueID: 372516

3-Methylcholanthrene elicits DNA adduct formation in the CYP1A1 promoter region and attenuates reporter gene expression in rat H4IIE cells. Keywords Mesh Terms:

KEYWORDS: Transfection

MESH TERMS: drug effects

Chemical & Substance for Abstract: 3-Methylcholanthrene elicits DNA adduct formation in the CYP1A1 promoter region and attenuates reporter gene expression in rat H4IIE cells. Information

Substance Name: Cytochrome P-450 CYP1A2

Registry Number: EC 1.14.14.1

Grant and Affiliation Information for 3-Methylcholanthrene elicits DNA adduct formation in the CYP1A1 promoter region and attenuates reporter gene expression in rat H4IIE cells.

AFFILIATION: Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA. bmoorthy@bcm.tmc.edu

Country: United States

AGENCY: United States NHLBI

GRANT: R01 HL070921

ACRONYM: HL

MEDLINETA: Biochem Biophys Res Commun

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