A Novel Photoadduct of 4,5',8‐trimethylpsoralen and Adenosine

Yun, Mi Hong; Choi, Seung Ju; Shim, Sang Chul

doi:10.1111/j.1751-1097.1992.tb04261.x

Cited by 12 publications

(3 citation statements)

References 13 publications

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“…These findings are in direct contrast to a previous study (25) in which PUVA-induced murine skin cancers harbored p53 mutations mainly at 5Ј-TpA sequences (also primary psoralen-binding sites and very likely targets of PUVA-induced mutagenesis) (5,6,(26)(27)(28). Indeed, cell culture studies have shown that in most cases PUVA leads to the formation of thymidine photoadducts or, much less frequently, of cytosine (29) or adenine photoadducts (30). Indeed, (repeated) AT sequences are hotspots for the photochemical reaction of 8-methoxypsoralen (8-MOP) with DNA, whose reactivity seems to increase in the following order: AT K TA ϳ TAT K ATA Ͻ ATAT Ͻ ATATAA (26,31,32).…”

Section: Introductioncontrasting

confidence: 91%

High Mutation Frequency at Ha-ras Exons 1-4 in Squamous Cell Carcinomas from PUVA-treated Psoriasis Patients¶

Kreimer-Erlacher¹,

Seidl²,

Bäck³

et al. 2007

Photochemistry and Photobiology

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Clinical follow-up studies have revealed that PUVAtreated patients are at increased risk of skin cancer, particularly squamous cell carcinoma (SCC). However, since psoralen and UVA (PUVA) is not only a potent mutagen and carcinogen but also an immunosuppressor, and since other (co)carcinogenic factors often exist in psoriasis patients, the exact causes and mechanisms of PUVA-associated SCC are still not completely understood. In order to fill this gap the tools of molecular epidemiology are being used to study the SCC mutational spectra of p53 and Ha-ras, two of the most commonly mutated genes in human cancers. A previous mutation analysis revealed that SCC in PUVA-treated patients often carried mutated p53 genes and that many of the mutations had the UV fingerprint (i.e. C→T or CC→TT transitions at dipyrimidine sites). In the present study DNA-sequencing analysis revealed a total of 18 Ha-ras missense or nonsense mutations at exons 1-4 in 13 of 17 SCC (76%) from 8 of 11 (73%) PUVA-treated psoriasis patients. Six of the 18 mutations (33%) were of UV-fingerprint type (C→T transitions), five (28%) were at 5-TpG sites (i.e. potential psoralen-binding sites and thus potentially caused by PUVA) and seven were of other type (39%), including six G:C→T:A transversions at hotspot codon 12. In addition, in the case of 6 of the 11 subjects (55%) both tumor and normal skin samples contained a T:A→C:G base change at codon 27 (a 5-ATT site), a change previously hypothesized to be a possible silent Ha-ras polymorphism at one allele. When we compared the present Ha-ras mutation spectrum with the p53 mutation spectrum from a previous study of the samples, we found that approximately half of the tumors harbored mutations in both Ha-ras and p53. Together, our results indicate that Ha-ras mutations are present in a large proportion of PUVA-associated SCC and that UVB, PUVA and other agents may induce Ha-ras mutations and act together with p53 in the formation of SCC in psoriasis patients. ¶Posted on the website on

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Section: Introductioncontrasting

confidence: 91%

High Mutation Frequency at Ha-ras Exons 1-4 in Squamous Cell Carcinomas from PUVA-treated Psoriasis Patients¶

Kreimer-Erlacher¹,

Seidl²,

Bäck³

et al. 2007

Photochemistry and Photobiology

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“…In another report we described the use of blue light (419 and 447 nm) for the photoactivation of 8-MOP to reduce XL formation to even lower levels (3% and 1%, respectively).' 8 We have also reported the results of different strategies for the targeting of psoralen photoadducts using oligodeoxyribonucleotides to induce the formation o f MA or XL a t a targeted base air.^','^…”

Section: Discussionmentioning

confidence: 99%

4′‐AMINOMETHYL‐4,5′,8‐TRIMETHYLPSORALEN PHOTOCHEMISTRY THE EFFECT OF CONCENTRATION AND UVA FLUENCE ON PHOTOADDUCT FORMATION IN POLY(dAdT) AND CALF THYMUS DNA

Oroskar

Olack

Peak

et al. 1994

Photochem & Photobiology

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The photochemistry of 4'-aminomethyl-4,5',8-trimethylpsoralen (AMT) with poly(dA-dT) and calf thymus DNA was studied. The extent of photoadduct formation and the distribution of photoadducts (3,4- and 4',5'-monoadducts and crosslinks) were determined by liquid scintillation analysis and HPLC, respectively. The adducts were characterized on the basis of their UV absorption spectra and mass spectral analysis. The high DNA binding constant for AMT (1.5 x 10(5) M-1) led to a high fraction of intercalated molecules, which contributed to the high level of AMT photoadduct formation, as many as 102 adducts per kilobase pair. In addition, there is a distinct difference in the adduct distribution compared to the previously studied 8-methoxypsoralen (8-MOP). Under the conditions employed for the photochemical studies, virtually all of the AMT molecules in solution are intercalated, occupying 25% of the base pair sites. Under similar conditions, 8-MOP molecules occupied 10 times fewer sites. Thus, for AMT, DNA base pair sites other than 5'TA, the well-characterized strong binding for psoralens in general, are an additional target for photomodification, which results in the formation of a higher percentage of monoadducts. The proportion of photoadducts formed was virtually independent of AMT concentration and UVA (320-400 nm radiation) fluence.

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“…It is reasonable to assume that photobiological effects of furocoumarins arise, at least partly, from a [2+2] photocycloaddition involving the 3,4double bond of the pyrone moiety and/or the 4',5'-double bond of the furan moiety of the psoralen on one hand and the 5,6-ethylenic bond of the DNA thymine residue on the other hand. The isolation and the characterization of the 5-MOP adducts to DNA bases have received far less attention as compared to those of 8-MOP and 4,5',8-TMP (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23). Preliminary photobinding studies showed that, within DNA, the furan-side photoadducts of several bifunctional furocoumarins are the predominant photoproducts whereas in the dry state, the pyrone-side photoadducts are formed preferentially.…”

Section: Introductionmentioning

confidence: 99%

Characterization of the cis-syn and cis-anti diastereoisomers of 5-methoxypsoralen pyrone-side monocycloadducts to thymidine

Anselmino

Voituriez²,

Cadet³

1993

Chem. Res. Toxicol.

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The photoreaction of 5-methoxypsoralen (5-MOP) with thymidine as a DNA model compound was investigated under dry-state conditions. In this respect, a thin film of thymidine and 5-MOP in a ratio 10:1 was exposed to 350-nm UV light. Four [2 + 2] photocycloadducts were isolated in a 0.5-2.2% yield with respect to 5-MOP by HPLC and characterized as two pairs of cis-syn and cis-anti diastereoisomers, respectively, on the basis of extensive spectroscopic measurements, including UV, fast atom bombardment mass spectrometry, 1H and 13C NMR, and CD. Information concerning the absolute configuration of the four photocycloadducts was inferred from detailed nuclear Overhauser enhancement experiments. This is indicative of a 3R,4S,5R,6S and a 3S,4R,5S,6R configuration for the cis-anti cycloadducts and a 3S,4R,5R,6S) and a 3R,4S,5S,6R configuration for the cis-syn cycloadducts. In addition, conformational features of the four photocycloadducts were obtained from consideration of various 1H NMR measurements including NOE data.

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A Novel Photoadduct of 4,5',8‐trimethylpsoralen and Adenosine

Cited by 12 publications

References 13 publications

High Mutation Frequency at Ha-ras Exons 1-4 in Squamous Cell Carcinomas from PUVA-treated Psoriasis Patients¶

High Mutation Frequency at Ha-ras Exons 1-4 in Squamous Cell Carcinomas from PUVA-treated Psoriasis Patients¶

4′‐AMINOMETHYL‐4,5′,8‐TRIMETHYLPSORALEN PHOTOCHEMISTRY THE EFFECT OF CONCENTRATION AND UVA FLUENCE ON PHOTOADDUCT FORMATION IN POLY(dAdT) AND CALF THYMUS DNA

Characterization of the cis-syn and cis-anti diastereoisomers of 5-methoxypsoralen pyrone-side monocycloadducts to thymidine

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