ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPreparation of the 8,9-epoxide mycotoxin aflatoxin B1: ultimate carcinogenic speciesSteven W. Baertschi, Kevin D. Raney, Michael P. Stone, and Thomas M. HarrisCite this: J. Am. Chem. Soc. 1988, 110, 23, 7929–7931Publication Date (Print):November 1, 1988Publication History Published online1 May 2002Published inissue 1 November 1988https://doi.org/10.1021/ja00231a083RIGHTS & PERMISSIONSArticle Views1353Altmetric-Citations193LEARN ABOUT THESE...

Acrolein and higher α,β-unsaturated aldehydes are bifunctional genotoxins. The deoxyguanosine adduct of acrolein, 3-(2-deoxy-β-d-erythro-pentofuranosyl)-5,6,7,8-tetrahydro-8-hydroxypyrimido[1,2-a]purin-10(3H)-one (8-hydroxy-1,N2-propanodeoxyguanosine, 2a), is a major DNA formed by acrolein. potential for oligodeoxynucleotide duplexes containing 2a to form interchain cross-links was evaluated HPLC, CZE, MALDI-TOF, melting phenomena. Interchain represent one the most serious types damage in...

Significant levels of the 1, N(2)-gamma-hydroxypropano-dG adducts alpha,beta-unsaturated aldehydes acrolein, crotonaldehyde, and 4-hydroxy-2E-nonenal (HNE) have been identified in human DNA, arising from both exogenous endogenous exposures. They yield interstrand DNA cross-links between guanines neighboring C.G G.C base pairs located 5'-CpG-3' sequences, as a result opening 1,N(2)-gamma-hydroxypropano-dG to form reactive that are positioned within minor groove duplex DNA. Using combination...

Real-world data from the first 3141 patients who completed 3 months of SmartGuard™ Auto Mode-enabled MiniMed™ 670G system use during MiniMed System Commercial Launch are reported. CareLink™ uploaded by real-world in March 17, 2017 to December 31, were deidentified and analyzed. Comparisons overall night (10:00 PM-07:00 AM) time spent below, within, above target glucose range (TIR) (70-180 mg/dL) between baseline Manual Mode closed-loop periods made. These evaluated alongside 124 (aged 14-75...

The mutagenic activity of the major DNA adduct formed by liver carcinogen aflatoxin B1 (AFB1) was investigated in vivo. An oligonucleotide containing a single 8,9-dihydro-8-(N7-guanyl)-9-hydroxyaflatoxin (AFB1-N7-Gua) inserted into single-stranded genome bacteriophage M13. Replication SOS-induced Escherichia coli yielded mutation frequency for AFB1-N7-Gua 4%. predominant G --> T, identical to principal human tumors believed be induced aflatoxin. T mutations AFB1-N7-Gua, unlike those (if...

Aflatoxin B1 (AFB1) is a known carcinogen associated with early-onset hepatocellular carcinoma (HCC) and thought to contribute over half million new HCCs per year. Although some of the fundamental risk factors are established, molecular basis AFB1-induced mutagenesis in primate cells has not been rigorously investigated. To gain insights into genome instability that produced as result replicating DNAs containing AFB1 adducts, site-specific assays were used establish mutagenic potential...

The primary DNA lesion induced by malondialdehyde, a byproduct of lipid peroxidation and prostaglandin synthesis, is 3-(2′-deoxy-β- d -erythro-pentofuranosyl)-pyrimido[1,2-a]purin-10(3H)-one (M 1 G). When placed opposite cytosine (underlined) at neutral pH in either the d(GGTMTCCG)⋅d(CGGA C ACC) or d(ATCGCMCGGCATG)⋅ d(CATGCCG GCGAT) duplexes, M G spontaneously quantitatively converts to ring-opened derivative N 2 -(3-oxo-1-propenyl)-dG. Ring-opening reversible on thermal denaturation. does...

The equilibrium binding of ethidium to the right-handed (B) and left-handed (Z) forms poly(dG-dC).poly(dG-dC) poly(dG-m5dC).poly(dG-m5dC) was investigated by optical phase partition techniques. Ethidium binds polynucleotides in a noncooperative manner under B-form conditions, sharp contrast highly cooperative Z-form conditions. Correlation isotherms with circular dichroism (CD) data indicates that conditions is associated sequential conversion polymer from conformation. Determination bound...

The oxidation of DNA resulting from reactive oxygen species generated during aerobic respiration is a major cause genetic damage that, if not repaired, can lead to mutations and potentially an increase in the incidence cancer aging. A product cells 8-oxoguanine (oxoG), which removed nucleotide pool by enzymatic hydrolysis 8-oxo-2′-deoxyguanosine triphosphate genomic 8-oxoguanine-DNA glycosylase. Finding repairing oxoG midst large excess unmodified requires combination rapid scanning for...

Formamidopyrimidines (Fapy) lesions result from ring opening of the imidazole portion purines. Fapy can isomerize natural β ‐anomeric stereochemistry to α ‐configuration. We have unambiguously demonstrated that ‐methyl‐Fapy‐dG (MeFapy‐dG) lesion is a substrate for Escherichia coli Endonuclease IV (Endo IV). Treatment MeFapy‐dG‐containing 24 mer duplex with Endo resulted in 36–40% incision. The catalytic efficiency incision was comparable ‐dG same sequence. ‐ and ‐MeFapy‐dG anomers...

5-Hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC) form during active demethylation of 5-methylcytosine (5mC) are implicated in epigenetic regulation the genome. They differentially processed by thymine DNA glycosylase (TDG), an enzyme involved 5mC. Three modified Dickerson-Drew dodecamer (DDD) sequences, amenable to crystallographic spectroscopic analyses containing 5'-CG-3' sequence associated with genomic cytosine methylation, 5hmC, 5fC, or 5caC placed...

Significance Human dietary exposures to aflatoxin in some of the most populated and underdeveloped portions world are a major contributing factor formation human hepatocellular carcinomas (HCCs) that account for over 700,000 deaths annually. Although genomic signatures aflatoxin-driven carcinogenesis G:C T:A point mutations arising from bypass aflatoxin-induced DNA adducts, maintenance genome stability has been generally attributed nucleotide excision repair. However, we present three lines...

Hepatocellular carcinomas (HCCs) are the third leading cause of cancer deaths worldwide. The highest rates early onset HCCs occur in geographical regions with high aflatoxin B1 (AFB1) exposure, concomitant hepatitis B infection. Although carcinogenic basis AFB1 has been ascribed to its mutagenic effects, property primary AFB1-DNA adduct, AFB1-N7-Gua, mammalian cells not studied extensively. Taking advantage ability create vectors containing a site-specific DNA potential was determined...

Objective: This study explored the outcome of applying red/near-infrared light therapy using light-emitting diodes (LEDs) pulsed with three different frequencies transcranially to treat traumatic brain injury (TBI) in Veterans. Background: Photobiomodulation (PBMT) LEDs has been shown have positive effects on TBI humans and animal models. Materials methods: Twelve symptomatic military Veterans diagnosed chronic >18 months post-trauma received transcranial PBMT (tPBMT) two neoprene pads...

8,9-Dihydro-8-(N7-guanyl-[d(ATCGAT)])-9-hydroxyaflatoxin B1.d(ATCGAT) and 8,9-dihydro-8-(N7-guanyl-[d(ATGCAT)])-9-hydroxyaflatoxin B1.8,9-dihydro-8-(N7-guanyl-[d(ATGCAT)])-9-hydroxyaflatoxin B1 were prepared by direct addition of afltoxin 8,9-epoxide to d(ATCGAT)2 d(ATGCAT)2, respectively. In contrast reaction aflatoxin with which exhibits a limiting stoichiometry 1:1 B1:d(ATCGAT)2 [Gopalakrishnan, S., Stone, M. P., & Harris, T. (1989) J. Am. Chem. Soc. 111, 7232-7239], d(ATGCAT)2 2:1...

Aflatoxin B1 (AFB) epoxide forms an unstable N7 guanine adduct in DNA. The undergoes base-catalyzed ring opening to give a highly persistent formamidopyrimidine (FAPY) which exists as mixture of forms. Acid hydrolysis the FAPY gives base two separable but interconvertible that have been assigned by various workers functional, positional, or conformational isomers. Recently, this structural question became important when one major species DNA was found be potently mutagenic and other block...

The working definition of health is often the simple absence diagnosed disease. This common standard limiting given that changes in functional status represent early warning signs impending declines. Longitudinal assessment may foster prevention disease occurrence and modify progression. LIFEHOUSE (Lifestyle Intervention Functional Evaluation-Health Outcomes SurvEy) longitudinal research project explores impact personalized lifestyle medicine approaches on determinants. Utilizing an adaptive...

Our studies examined the role of dopamine D4 receptors in induction behavioral sensitization to amphetamine (Amp) and accompanying neurochemical molecular adaptive responses using a highly selective antagonist, PNU-101387G. Behavioral an acute challenge Amp (2 mg/kg, s.c.) was observed rats pretreated with five daily doses mg/kg/d, followed by 7-day withdrawal. Interestingly, coadministration PNU-101387G during pretreatment completely blocked sensitized response challenge. The its blockade...

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDNA conformation mediates aflatoxin B1-DNA binding and the formation of guanine N7 adducts by B1 8,9-exo-epoxideVeronica M. Raney, Thomas Harris, Michael P. StoneCite this: Chem. Res. Toxicol. 1993, 6, 1, 64–68Publication Date (Print):January 1993Publication History Published online1 May 2002Published inissue 1 January 1993https://pubs.acs.org/doi/10.1021/tx00031a010https://doi.org/10.1021/tx00031a010research-articleACS PublicationsRequest reuse...

The solution structure of the oligodeoxynucleotide 5'-d(CTCGGCXCCATC)-3'·5'-d(GATGGCGCCGAG)-3' containing heterocyclic amine 8-[(3-methyl-3H-imidazo[4,5-f]quinolin-2-yl)amino]-2'-deoxyguanosine adduct (IQ) at third guanine in NarI restriction sequence, a hot spot for −2 bp frameshifts, is reported. Molecular dynamics calculations restrained by distances derived from 24 1H NOEs between IQ and DNA, torsion angles 3J couplings, yielded ensembles structures which adducted was displaced into...

The exocyclic DNA adduct 1,N2-propano-2'-deoxyguanosine (PdG) was inserted into the oligodeoxynucleotide 5'-CGC(PdG)CGGCATG-3' and annealed to complementary 5'-CATGCCGCGCG-3'. This sequence is derived from a spontaneous revertant of hisD3052 gene in frameshift-sensitive tester strain Salmonella typhimurium hotspot for two-base pair deletions. solution structure modified duplex examined by 1H NMR spectroscopy. lesions resulted loss Watson-Crick base-pairing capability. Modification an...

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPreparation and characterization of an aflatoxin B1 adduct with the oligodeoxynucleotide d(ATCGAT)2S. Gopalakrishnan, Michael P. Stone, Thomas M. HarrisCite this: J. Am. Chem. Soc. 1989, 111, 18, 7232–7239Publication Date (Print):August 1, 1989Publication History Published online1 May 2002Published inissue 1 August 1989https://pubs.acs.org/doi/10.1021/ja00200a051https://doi.org/10.1021/ja00200a051research-articleACS PublicationsRequest reuse...

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTInteraction of drugs with Z-DNA: cooperative binding actinomycin D or actinomine to the left-handed forms poly(dG-dC).cntdot.poly(dG-dC) and poly(dG-m5dC).cntdot.poly(dG-m5dC) reverses conformation helixG. Terrance Walker, Michael P. Stone, Thomas R. KrughCite this: Biochemistry 1985, 24, 25, 7471–7479Publication Date (Print):December 1, 1985Publication History Published online1 May 2002Published inissue 1 December...