Chromosome-damaging effects of heraclenin in human lymphocytes in vitro

Abel, G.; Schimmer, Oskar

doi:10.1016/0165-1218(86)90018-2

Cited by 17 publications

(9 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…They have been reported to cause a variety of beneficial [Pathal and Fitzpatrick 1992;Kim et al, 2007;] and harmful [Abel et al, 1986] effects. In present study, we showed the positive data by demonstrat- ing that NOFs such as imperatorin, isoimperatoirn, (1)-oxypeucedanin, (1)-byakangelicol, and (1)-byakangelicine can inhibit procarcinogen-induced SOS responses in the S. typhimurium TA1535/pSK1002 strain (umu test).…”

Section: Discussionmentioning

confidence: 99%

Antigenotoxic activity of naturally occurring furanocoumarins

Marumoto

Oda

Miyazawa

2011

Environ. Mol. Mutagen.

View full text Add to dashboard Cite

This study was designed to investigate the antigenotoxic effects of a series of naturally occurring furanocoumarins (NOFs) including isoimperatorin, imperatorin, (+)-oxypeucedanin, (+)-byakangelicol, and (+)-byakangelicine on antigenotoxic activities against genotoxicity induced by carcinogens [furylfuramide and N-methyl-N'-nitro-N-nitrosoguanidine], and procarcinogens 2-[2-(acetylamino)-4-amino-5-methoxyphenyl]-5-amino-7-bromo-4-chloro-2H-benzotriazole (PBTA-4) and 2-amino-3,4-dimethyl-3H-imidazo-[4,5-f] quinoline (MeIQ)] to genotoxic metabolites catalyzed by rat S9 or rat and human recombinant cytochrome P450 (CYP) 1As by using the umu test based on SOS response. Five different NOFs, which were found in the human diets, strongly inhibited the umuC induction by procarcinogens, but did not be affected by carcinogens. Notably, isoimperatorin and (+)-byakangelicol were found to be potent inhibitors on the metabolic activation of PBTA-4 and MeIQ to genotoxic metabolites catalyzed by rat and human CYP1A1, or rat and human CYP1A2, respectively. In addition, to elucidate the mechanism of their antigenotoxic effects against procarcinogens, the effects of NOFs on rat and human CYP1A1- or rat and human CYP1A2-related enzyme activities of 7-ethoxyresorufin-O-deethylase (EROD) were also investigated. Reduction of the EROD activities by some of the NOFs with IC(50) values of 0.23-20.64 μM was found to be due to strong inhibition of CYP1A1 and CYP1A2 dependent monooxygenases. Furthermore, the mechanism of inhibitions by NOFs on human CYP1A1 and CYP1A2 was analyzed by means of Dixon plots plus Cornish-Bowden plots. The kinetic studies of inhibition types revealed that these compounds inhibited the human CYP1A1 and CYP1A2 a variety of modes rather than by a uniform one. Moreover, experiments with a two-stage incubation indicated that NOFs, except for imperatorin, inhibited human CYP1A1 in a mechanism-based manner, but directly inhibited human CYP1A2. This data suggest that certain NOFs, to which humans are exposed in the diet, may be capable of affecting the metabolic activation of procarcinogens due to inhibitions of CYP1A1 and CYP1A2 enzymes.

show abstract

Section: Discussionmentioning

confidence: 99%

Antigenotoxic activity of naturally occurring furanocoumarins

Marumoto

Oda

Miyazawa

2011

Environ. Mol. Mutagen.

View full text Add to dashboard Cite

show abstract

“…Reports about the mutagenicity of heraclenin are conflicting. No mutagenic effects were observed in Salmonella typhimurium [124], but marked chromosomal damage (structural chromosome aberrations and sister-chromatid exchanges) were revealed in human lymphocytes in vitro [125]. Finally heraclenin, unlike imperatorin, was weakly effective as an anti-HIV agent (IC 50 Byakangelicin (47) inhibits aldose reductase (IC 50 = 6.2 µM), therefore it may prove useful for the prevention and treatment of diabetic or age-related cataract [130][131][132].…”

Section: Very Recently Appendino and Coworkers Showed That Imperatorimentioning

confidence: 99%

Chemistry and Biological Activity of Natural and Synthetic Prenyloxycoumarins †

Curini¹,

Cravotto²,

Epifano³

et al. 2006

CMC

274

170

View full text Add to dashboard Cite

Prenyloxycoumarins and prenyloxyfuranocoumarins (isopentenyloxy-, geranyloxy-, linear and cyclic sesquiterpenyloxy compounds and their biosynthetic derivatives) represent a family of secondary metabolites that have been considered for years just as intermediates of other coumarin-based compounds. Only in the last two decades these secondary metabolites have been recognized as interesting and valuable biologically active natural products. Up to now more than 160 compounds have been isolated from plants mainly belonging to the families of Rutaceae and Umbelliferae, comprising common edible vegetables and fruits like lemons, oranges and grapefruits. In view of the biological activity of some natural prenyloxycoumarins, very recently syntheses of structurally related analogs aimed to establish detailed structure-activity relationships have also been carried out. Many of the isolated prenyloxy- and prenyloxy-furanocoumarins and their semisynthetic derivatives were shown to exert in vitro and in vivo remarkable anti-tumoral, anti-inflammatory and anti-viral effects. The object of this review is to examine in detail the different types of prenyloxycoumarins and prenyloxyfuranocoumarins from the chemical, phytochemical and biological point of view.

show abstract

“…Heraclenin, a linear furanocoumarin with an epoxidic structure in its side chain, was a weak mutagen in bacteria (Ivie et al, 1980) but a strong clastogen in human lymphocytes (Abel and Schimmer, 1986). The photobiology and the genetic basis of furanocoumarin reactions were reviewed by Scott and co-workers (1976), Song and Tapley (1979), Averbeck (1989) and in an IARC report (1986).…”

Section: Salmonella Typhimuriummentioning

confidence: 99%

Molecular Modes of Action of Defensive Secondary Metabolites

Wink

Schimmer

2010

Functions and Biotechnology of Plant Secondary Metabolites

Self Cite

View full text Add to dashboard Cite

Secondary metabolites (SM) have been shaped by evolution for more than 500 million years. As a result, many of them have distinctive biochemical and pharmacological properties. The molecular modes of action of the main groups of SM are reviewed in this chapter. Details are given on interactions of SM with proteins that can induce conformational changes and thus a modification of their bioactivity. The fluidity and permeability of biomembranes constitute another important target, which is influenced by many lipophilic and amphiphilic SM. A number of SM can either alkylate or intercalate DNA, which can cause mutations and in consequence cancer or malformations. Many SM are cytotoxic because they interfere with biomembranes, proteins of the cytoskeleton or DNA; they often induce programmed cell death (apoptosis). A large number of SM, especially alkaloids modulate neuronal signal transduction by interfering with ion channels, ion pumps, neuroreceptors, choline esterase, monoamine oxidase and other enzymes related to signal transduction pathways. A typical feature of SM is their ability to modulate more than one molecular target; thus, additive and even synergistic activities can be expected.

show abstract

Chromosome-damaging effects of heraclenin in human lymphocytes in vitro

Cited by 17 publications

References 11 publications

Antigenotoxic activity of naturally occurring furanocoumarins

Antigenotoxic activity of naturally occurring furanocoumarins

Chemistry and Biological Activity of Natural and Synthetic Prenyloxycoumarins †

Molecular Modes of Action of Defensive Secondary Metabolites

Contact Info

Product

Resources

About