Studies on carcinogen chromatin-DNA interaction: inhibition of N-methyl-N-nitrosourea-induced methylation of chromatin-DNA by spermine and distamycin A

Rajalakshmi, S.; Rao, Prema M.; Sarma, D.S.R.

doi:10.1021/bi00614a024

Cited by 45 publications

(23 citation statements)

References 18 publications

(15 reference statements)

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“…The level of DNA methylation was inversely dependent on salt concentration and the binding affinity of the cation; however, the methylation pattern itself remained unperturbed ( Figure 3). Other laboratories observed an inhibitory effect of distamycin A on adduct yields, but attributed the inhibition to its minor groove binding properties (52). However, we showed that the effect was on both major and minor groove products, and that the former inhibition was independent of sequence while the latter occurred at distamycin A equilibrium binding sites (53).…”

Section: Effect Of Salt On Dna Alkylationcontrasting

confidence: 51%

A Review of the Role of the Sequence-Dependent Electrostatic Landscape in DNA Alkylation Patterns

Gold

Marky

Stone

et al. 2006

Chem. Res. Toxicol.

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Alkylating agents, including environmental and endogenous carcinogens, and DNA targeting antineoplastic agents, that adduct DNA via intermediates with significant cationic charge show a sequence selectively in their covalent bonding to nucleobases. The resulting patterns of alkylation eventually contribute to the agent-dependent distributions and types of mutations. The origin of the regioselective modification of DNA by electrophiles has been attributed to steric and/or electronic factors, but attempts to mechanistically model and predict alkylation patterns have had limited success. In this review, we present data consistent with the role of the intrinsic sequence-dependent electrostatic landscape (SDEL) in DNA that modulates the equilibrium binding of cations and the bonding of reactive charged alkylating agents to atoms that line the floor of the major groove of DNA.

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Section: Effect Of Salt On Dna Alkylationcontrasting

confidence: 51%

A Review of the Role of the Sequence-Dependent Electrostatic Landscape in DNA Alkylation Patterns

Gold

Marky

Stone

et al. 2006

Chem. Res. Toxicol.

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“…It has previously been shown that spermidine, which binds to A-T sites in DNA, can inhibit methylation of rat liver chromatin in a dose-dependent way (31). In those studies MeNU was the methylating agent and 90%o inhibition occurred with 0.10 mM spermidine and 2.0 mM MeNU in the presence of 0.6 mM (nucleotide) chromatin or DNA.…”

Section: Resultsmentioning

confidence: 93%

“…The interpretation of these data was that the spermidine inhibition is specific for duplex DNA because of its unique structure. Distamycin A, a DNA minor-groove binder that has an affinity for A+T-rich sites (32), also inhibited guanine methylation in a dose-dependent manner (31). This (34), and it does show some preference for A+T-rich sequences.…”

Section: Resultsmentioning

confidence: 98%

“…Both of these sites face into the major groove. However, the minor-groove binders distamycin and spermidine also inhibit methylation at these two major groove sites (31). It is possible that ellagic acid may indirectly inhibit the methylation reaction by altering the conformation of DNA near its binding site(s) so as to make the major groove 06 atom less accessible to the methylating species.…”

Section: Resultsmentioning

confidence: 99%

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Inhibition of N-methyl-N-nitrosourea-induced mutagenicity and DNA methylation by ellagic acid.

Dixit¹,

Gold²

1986

Proc. Natl. Acad. Sci. U.S.A.

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Ellagic acid, a naturally occurring plant phenol, inhibits the activity of the direct-acting mutagen N-methyl-N-nitrosourea (MeNU) in Salmonella typhimurium TA100.Ellagic acid at 0.10, 0.25, 0.50, and 1.00 mM inhibited the mutagenicity of MeNU (0.40 mM) by 3%, 13%, 45%, and 60%, respectively. Ellagic acid (3 mM) also inhibited the mutagenic activity of in the presence of pyrazole-induced rat liver fraction S-9. The effect of ellagic acid on DNA methylation was studied by incubating 0, 0.72, 1.32, 2.64, and 6.60 mM ellagic acid with DNA (0.9 mM nucleotide) and PHJMeNU (0.66 mM). HPLC analysis of DNA hydrolysates showed that ellagic acid caused a dose-dependent 36-84% decrease in 06-methylguanine but only a 20% decrease in the 7-methylguanine adduct. Under conditions where methylation at the 06 position of guanine in double-stranded DNA was inhibited 65% by ellagic acid, no significant inhibition of either 06-or 7-methylguanine formation was detected in single-stranded DNA. Affinity-binding studies revealed that [3H]eilagic acid binds equally to doublestranded or single-stranded DNA but that poly(dA dT) binds 1.5 times as much ellagic acid as does poly(dG-dC). The binding of ellagic acid to DNA is dependent on the concentration of both ellagic acid and DNA. The specific inhibition of 06. methylguanine formation only in double-stranded DNA and the relatively low inhibition of 7-methylguanine formation rule out the possibility that ellagic acid prevents DNA alkylation by scavenging the electrophilic intermediate generated in the hydrolysis of MeNU. The results suggest that ellagic acid inhibition of MeNU-induced mutagenicity is due to specific inhibition of methylation at the 06 position of guanine through an ellagic acid-duplex DNA afflnity-binding mechanism.Ellagic acid (2,3,7,8-tetrahydroxy[J]benzopyrano [5,4,3-cde][J]benzopyran-5,10-dione), a natural product shikimate derivative present in soft fruits and vegetables (1-3), inhibits the carcinogenicity of benzo[a]pyrene (B[a]P) (4) and the carcinogenicity and mutagenicity (5-8) and DNA binding (9, 10) of benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE), an activated form of B[a]P. It was suggested that the chemopreventive activity of ellagic acid results from its ability to accelerate the detoxification of BPDE by forming a BPDE-ellagic acid adduct (11). It was further suggested that the reason for the rapid reaction between BPDE and ellagic acid resulted from an initial ir-7r nonbonded interaction. The apparent second-order rate constant for the disappearance of BPDE at pH 7.0 is more than 300-fold faster in the presence of ellagic acid (11). In summary, the proposed antimutagenic and antitumorigenic activity of ellagic acid was suggested to result from its direct interception of the "ultimate" electrophilic form of B[a]P, thereby preventing DNA adduction.While this mechanism may be effective with the reactive electrophiles generated in the metabolism of polycyclic aromatic hydrocarbons, it is not likely that such a "scavenging" mechanism would be eff...

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“…Polyamines also have anti-oxidant, radical scavenger properties and other biological activities that help protect cells and genes from harmful stimuli (Belle et al, 2004;Brune et al, 1991;Chattopadhyay et al, 2003;Chiu & Oleinick, 1998;Douki et al, 2000;Farbiszewski et al, 1996;Fujisawa & Kadoma, 2005;Gaboriau et al, 2005;Goss et al, 1995;Ha, Sirisoma, et al, 1998;Ha, Yager, et al, 1998;Held & Awad, 1991;Khan et al, 1992;Lovaas & Carlin, 1991;Marzabadi & Llvaas, 1996;Newton et al, 1996Newton et al, , 1997Rajalakshmi et al, 1978;Sava et al, 2006;Soda et al, 2005;Spotheim-Maurizot et al, 1995;Sy et al, 1999;Tadolini, 1988;Tadolini et al, 1984;Warters et al, 1999;Zhang et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Biological Effects of Polyamines on the Prevention of Aging-associated Diseases and on Lifespan Extension

Soda

2015

FSTR

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Studies on carcinogen chromatin-DNA interaction: inhibition of N-methyl-N-nitrosourea-induced methylation of chromatin-DNA by spermine and distamycin A

Cited by 45 publications

References 18 publications

A Review of the Role of the Sequence-Dependent Electrostatic Landscape in DNA Alkylation Patterns

A Review of the Role of the Sequence-Dependent Electrostatic Landscape in DNA Alkylation Patterns

Inhibition of N-methyl-N-nitrosourea-induced mutagenicity and DNA methylation by ellagic acid.

Biological Effects of Polyamines on the Prevention of Aging-associated Diseases and on Lifespan Extension

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