scholarly journals Metabolic Activation of the Tumorigenic Pyrrolizidine Alkaloid, Retrorsine, Leading to DNA Adduct Formation In Vivo

2005 ◽  
Vol 2 (1) ◽  
pp. 74-79 ◽  
Author(s):  
Yu-Ping Wang ◽  
Peter Fu ◽  
Ming Chou
Keyword(s):  
Pyrrolizidine Alkaloid ◽  
Metabolic Activation ◽  
Adduct Formation ◽  
Dna Adduct

Metabolic activation of the tumorigenic pyrrolizidine alkaloid, monocrotaline, leading to DNA adduct formation in vivo

2005 ◽  
Vol 226 (1) ◽  
pp. 27-35 ◽  
Author(s):  
Yu-Ping Wang ◽  
Jian Yan ◽  
Richard D. Beger ◽  
Peter P. Fu ◽  
Ming W. Chou
Keyword(s):  
Pyrrolizidine Alkaloid ◽  
Metabolic Activation ◽  
Adduct Formation ◽  
Dna Adduct

Metabolic Activation of the Tumorigenic Pyrrolizidine Alkaloid, Riddelliine, Leading to DNA Adduct Formation in Vivo

2001 ◽  
Vol 14 (1) ◽  
pp. 101-109 ◽  
Author(s):  
Ya-Chen Yang ◽  
Jian Yan ◽  
Daniel R. Doerge ◽  
Po-Cheun Chan ◽  
Peter P. Fu ◽  
...  
Keyword(s):  
Pyrrolizidine Alkaloid ◽  
Metabolic Activation ◽  
Adduct Formation ◽  
Dna Adduct

scholarly journals Ellipticine and benzo(a)pyrene increase their own metabolic activation via modulation of expression and enzymatic activity of cytochromes P450 1A1 and 1A2

2008 ◽  
Vol 1 (2) ◽  
pp. 160-168 ◽  
Author(s):  
Dagmar Aimová ◽  
Jitka Poljaková ◽  
Věra Kotrbová ◽  
Michaela Moserová ◽  
Eva Frei ◽  
...  
Keyword(s):  
Enzymatic Activity ◽  
Dna Adducts ◽  
Cytochromes P450 ◽  
Antineoplastic Agent ◽  
Metabolic Activation ◽  
Experimental Models ◽  
Adduct Formation ◽  
Dna Adduct

Ellipticine and benzo(a)pyrene increase their own metabolic activation via modulation of expression and enzymatic activity of cytochromes P450 1A1 and 1A2Two compounds known to covalently bind to DNA after their activation with cytochromes P450 (CYPs), carcinogenic benzo(a)pyrene (BaP) and an antineoplastic agent ellipticine, were investigated for their potential to induce CYP and NADPH:CYP reductase (POR) enzymes in rodent livers, the main target organ for DNA adduct formation. Two animal models were used in the study: (i) rats as animals mimicking the fate of ellipticine in humans and (ii) mice, especially wild-type (WT) and hepatic POR null (HRN™) mouse lines. Ellipticine and BaP induce expression of CYP1A enzymes in livers of experimental models, which leads to increase in their enzymatic activity. In addition, both compounds are capable of generating DNA adducts, predominantly in livers of studied organisms. As determined by32P postlabelling analysis, levels of ellipticine-derived DNA adducts formedin vivoin the livers of HRN™ mice were reduced (by up to 65%) relative to levels in WT mice, indicating that POR mediated CYP enzyme activity is important for the activation of ellipticine. In contrast to these results, 6.4 fold higher DNA binding of BaP was observed in the livers of HRN™ mice than in WT mice. This finding suggests a detoxication role of CYP1A in BaP metabolismin vivo. Inin vitroexperiments, DNA adduct formation in calf thymus DNA was up to 25 fold higher in incubations of ellipticine or BaP with microsomes from pretreated animals than with controls. This stimulation effect was attributed to induction of CYP1A1/2 enzymes, which are responsible for oxidative activation of both compounds to the metabolites generating major DNA adductsin vitro. Taken together, these results demonstrate that by inducing CYP1A1/2, ellipticine and BaP modulate their own enzymatic metabolic activation and detoxication, thereby modulating their either pharmacological (ellipticine) and/or genotoxic potential (both compounds).

Human Liver Microsomal Metabolism and DNA Adduct Formation of the Tumorigenic Pyrrolizidine Alkaloid, Riddelliine

2003 ◽  
Vol 16 (1) ◽  
pp. 66-73 ◽  
Author(s):  
Qingsu Xia ◽  
Ming W. Chou ◽  
Fred. F. Kadlubar ◽  
Po-Cheun Chan ◽  
Peter P. Fu
Keyword(s):  
Human Liver ◽  
Pyrrolizidine Alkaloid ◽  
Adduct Formation ◽  
Dna Adduct ◽  
Microsomal Metabolism

DNA adduct formation by O-phenylphenol metabolite in vivo and in vitro

1992 ◽  
Vol 13 (8) ◽  
pp. 1469-1473 ◽  
Author(s):  
Keiko Ushiyama ◽  
Fumiko Nagai ◽  
Atsuko Nakagawa ◽  
Itsu Kano
Keyword(s):  
Adduct Formation ◽  
Dna Adduct
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