The hepatic metabolism of ethidium bromide to reactive mutagenic species: biochemical and structural requirements

Lecointe, P.; Bichet, N.; Fraire, Claudine; Paoletti, Claude

doi:10.1016/0006-2952(81)90132-5

Cited by 25 publications

(10 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, as previously shown in adult male, Sprague Dawley rats, 3-methylcholanthrene pretreatment, in contrast to phenobarbitone, did not induce either aminopyrine N-demethylase or aniline hydroxylase (Iba & Sikka 1983). It also enhanced the enzymatic activation of ethidium bromide to reactive mutagenetic species as demonstrated by Lecointe et al (1981), as also reported for P-naphthoflavone and 3-methylcholanthrene (Lesca et al 1984). Like phenobarbitone, Arochlor pretreatment caused a significant increase in aminopyrine N-demethylase, aniline hydroxylase and NADPH cytochrome c reductase.…”

Section: Resultssupporting

confidence: 71%

Induction of drug metabolizing enzymes in the liver of rats infested with Fasciola hepatica

Galtier

Larrieu

Lesca

1985

Journal of Pharmacy and Pharmacology

View full text Add to dashboard Cite

Adult, male rats were infected with 20 metacercariae of Fasciola hepatica given orally, other rats were left untreated. Five weeks after infestation, some animals received phenobarbitone, 3-methylcholanthrene, beta-naphthoflavone or Arochlor 1254, to induce liver drug metabolizing enzymes. Fascioliasis provoked decreases in aminopyrine N-demethylase, aniline hydroxylase, the mutagenic activity of cyclophosphamide and cytochrome P-450 concentration in untreated or phenobarbitone or Arochlor pretreated rats. In contrast, cytochrome b5, NADPH cytochrome c reductase, ethyoxycoumarin O-deethylase and the enzymatic activation of ethidium bromide were not affected by fascioliasis whatever pretreatment was given. Fascioliasis decreased liver drug metabolizing enzymes which were specifically induced by both phenobarbitone and Arochlor, this could be due to either the specific action of toxic excretions of flukes or to the particular localization of tissue damage within the liver lobule.

show abstract

Section: Resultssupporting

confidence: 71%

Induction of drug metabolizing enzymes in the liver of rats infested with Fasciola hepatica

Galtier

Larrieu

Lesca

1985

Journal of Pharmacy and Pharmacology

View full text Add to dashboard Cite

show abstract

“…Protons H 1 and H 10 are meta to each amine and exhibit little sensitivity to Cbz modification. Protons H 2 , H 4 , H 7 , and H 9 , on the other hand, are all ortho to the exocyclic amines; but protons H 4 and H 7 are shifted downfield by 1.4 ppm, while H 2 and H 9 are only shifted downfield by 0.7 ppm upon Cbz modification of the neighboring amine (compare compounds 2 and 3 to compound 1, Figure 6a, b, and d). This same effect is also apparent in the 13 C NMR spectra of these compounds (next section).…”

Section: Photophysical Propertiesmentioning

confidence: 92%

“…[4,5] Its potential applications in human therapy are prevented, however, due to its mutagenic and carcinogenic activities in model organisms. [6,7] These activities are thought to be a direct consequence of ethidiums high affinity for DNA. [8][9][10] We recently derivatized the amines at the 3-and 8-positions of ethidium to tune its nucleic acid affinity and binding specificity.…”

Section: Introductionmentioning

confidence: 99%

On the Electronic Structure of Ethidium

Luedtke

Liu

Tor

2004

Chemistry A European J

View full text Add to dashboard Cite

The electronic structure of the common intercalating agent ethidium bromide (3,8-diamino-5-ethyl-6-phenylphenanthridinium bromide) is dominated by an interplay of electron donating and withdrawing effects mediated by its nitrogen atoms. X-ray crystallography, UV/Vis and IR absorption, fluorescence emission, and NMR spectroscopy are used to probe the electronic properties of the phenanthridinium "core" of ethidium as well as its exocyclic amines and 6-phenyl groups. Interestingly, despite its positive charge, most of ethidium's aromatic carbon and hydrogen atoms have high electron densities (compared to both 6-phenylphenanthridine and benzene). The data suggest that electron donation by ethidium's exocyclic amines dominates over the electron withdrawing effects of its endocyclic iminium in their combined influence on the electron densities of these atoms. Ethidium's nitrogen atoms are, conversely, electron deficient where the 5-position is the most electropositive, followed by the 3-amino, and lastly the 8-amino group. These results have been used to generate an empirically-based pi-electron density map of ethidium that may prove useful to understanding its nucleic acid binding specificity.

show abstract

“…Ethidium (figure 1b), on the other hand, has been a universal fluorescent probe and DNA staining agent developed as an anti-trypanosmal agent [29][30][31]. It is a frame shift mutagen [32] but has antiviral, antibacterial and anti cancer properties as well 0021-9614/$ -see front matter Ó 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.jct.2010.05.005 [33,34].…”

Section: Introductionmentioning

confidence: 99%

Thermodynamic profiles of the DNA binding of benzophenanthridines sanguinarine and ethidium: A comparative study with sequence specific polynucleotides

Hossain

Kumar

2010

The Journal of Chemical Thermodynamics

View full text Add to dashboard Cite

The hepatic metabolism of ethidium bromide to reactive mutagenic species: biochemical and structural requirements

Cited by 25 publications

References 19 publications

Induction of drug metabolizing enzymes in the liver of rats infested with Fasciola hepatica

Induction of drug metabolizing enzymes in the liver of rats infested with Fasciola hepatica

On the Electronic Structure of Ethidium

Thermodynamic profiles of the DNA binding of benzophenanthridines sanguinarine and ethidium: A comparative study with sequence specific polynucleotides

Contact Info

Product

Resources

About