摘要:

Abstract—The tetracyclic furocoumarin 2H‐benzofuro[3,2‐g]‐1‐benzo‐pyran‐2‐one and its 4 and/or II methyl analogues have been investigated in their DN A‐photobinding properties. Spectrophotometric and radioactivity measurements show that these compounds exhibit prominent ability to bind to the polynucleotide double helix by covalent photoaddition of the furocoumarin 3,4 double bond.Denaturation‐renaturation experiments demonstrate that no cross‐link of DNA chains occurs. Benzopsoralens can thus be considered as a new class of monofunctional DN

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1986.tb03555.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

Abstract—Using the spin‐trapping technique we have investigated the photolysis of chlorpromazine sulfoxide and promazine sulfoxide. Photolysis of these sulfoxides in aqueous solution resulted in a species which is capable of oxidizing ascorbate, cysteine, glutathione, NADH, and azide by one electron, in addition to extracting hydrogen atoms from ethyl alcohol and dimethyl sulfoxide. These oxidations were not dependent on the presence of dissolved oxygen. The oxidizing species is proposed to be the hydroxyl free radical arising from the homolytic cleavage of the S‐O bond of the sulfoxide. Flash photolysis of the chlorpromazine and promazine sulfoxides demonstrated the formation of cation radicals consistent with the loss of the hydroxyl radical from the sulfoxides. In addition we present a simple direct method for the quantitative synthesis of promazine and chlorpromazine sulfoxides from the parent promazine deriva

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1986.tb03556.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

Abstract—The transient absorbance observed after flash excitation of a well characterized humic substance (“Armadale” fulvic acid) may be analyzed into three components. Two arise promptly (<20 ps) and are assigned to a solvated electron (on the basis of decay and quenching) and its corresponding radical cation (on the basis of common origin). The third is a broad featureless band which arises only after a few ns and remains for long times. It is suggested to include triplets that may sensitize singlet o

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1986.tb03557.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

Abstract—Human cells of the line NHIK 3025 were exposed to hematoporphyrin derivative (Hpd) and light and analysed with respect to; (i) the mobility of membrane proteins as determined by electron spin resonance measurements of a protein‐bound spin label, (ii) fluorescence excitation spectra, (iii) relative number of DTNB‐reactive SH‐groups on their surface and in sonicated cell homogenates, (iv) survival, and (v) morphologic appearance as seen by ordinary phase contrast microscopy. A significant fraction of the porphyrins bound to the outer cell membrane was in close contact with proteins. 5,5′‐Dithiobis‐2‐nitrobenzoic acid reactive SH‐groups on the outer cell membrane were very sensitive to the treatment with Hpd + light and were degraded according to non‐exponential kinetics. When the cells were irradiated after spin labelling, the labelled proteins became less mobile during the irradiation, indicating protein cross linking. Irradiation before spinlabelling resulted in a selective degradation of lo

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1986.tb03558.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

Abstract—We have investigated the site specificity of furocoumarins by using fluorescent densitometry to examine the frequency of cleavage by the restriction enzyme Bgl I. This enzyme has an 11 base pair (bp) recognition sequence which varies slightly from site to site because it includes a 5 base pair neutral region. Cleavage at all three Bgl I recognition sites in pBR322 was inhibited by the photoaddition of the psoralen derivative 4′‐hydroxymethyl‐4,5′,8‐trimethylpsoralen (HMT) which forms both crosslinks and monoad‐ducts in a dose‐dependent manner. One site, which contains two thymidines in a crosslinkable configuration, was observed to be markedly more sensitive to HMT photoadducts. In contrast Bgl I cleavage at all sites was relatively resistant to the derivative 5‐methylisopsoralen (5‐MIP), which forms only monoadducts. When HMT‐reacted DNA was generated with widely different ratios of monoad‐ducts to crosslinks (3% and 40% crosslinks), essentially the same level and pattern of inhibition was observed in both cases. Taken together, the data imply that differences in inhibition seen at the three cutting sites of Bgl I with HMT are attributable to DNA sequence and the role it play

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1986.tb03559.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

Abstract—The photobiological activity of the two monofunctional pyridopsoralens pyrido (3,4‐c) psoralen (PyPs) and 7‐methyl pyrido (3,4‐c) psoralen (MePyPs) was studied in mammalian cellsin vitrotaking 8‐methoxypsoralen (8‐MOP) as a reference compound.In the presence of 365‐nm irradiation (UVA) MePyPs was found to be more effective than 8‐MOP in terms of DNA photobinding capacity and inhibition of cell cloning ability in Chinese hamsterV–79 cells. As a function of UVA dose and of the number of total photoadducts induced MePyPs produced a higher frequency of 6‐thioguanine resistant mutants than 8‐MOP. PyPs showed an intermediate response for cell killing and mutation induction. At equal cytotoxic levels both monofunctional pyridopsoralens exhibited the same mutagenic activity as the Afunctional furocoumarin 8‐MOP.The antiproliferative effect being taken as indicative for an efficient photochemotherapeutic activity against psoriasis, the inhibition of cloning capacity induced by MePyPs plus UVA was studied in parallel on human skin fibroblasts. Such cells were more sensitive to 8‐MOP photoadditions thanV–79 cells and even more so to MePyPs photoadditions. Data obtained on the rate of DNA semi conservative synthesis on both cell lines following treatments with the two compounds are in l

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1986.tb03560.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

Abstract—Photobinding of sulfanilamide to bovine serum albumin (BSA) was investigated by irradiating BSA and buffered BSA/drug solutions with UV light (Λ= 300 nm) under anaerobic conditions. The protein solutions were then denatured and the unbound sulfanilamide removed. Marked differences in the UV and fluorescence spectra of the solutions before and after irradiation were observed, suggesting covalent binding of the drug to BSA. This was confirmed using [14C]labelled sulfanilamide. The extent of photobinding of sulfanilamide determined using the radiolabeled drug, was concentration dependent. The binding ratio varied from 3 mol drug per mol BSA for a 10‐4Mdrug concentration, to 10 mol drug per mol BSA for 10‐2Mdrug concentration.The protein solutions were hydrolysed under acid conditions and the amino acids obtained were analysed by ion exchange chromatography. The hydrolysate of irradiated BSA (10‐4M) ‐sulfanilamide (10‐2M) mixture lost about 10 mol of cystine per mol of BSA. This loss was not observed after hydrolysis of irradiated alone or non‐irradiated BSA. Irradiation of cystine with [14C]sulfanilamide in HC1 solutions produced the same compound as was found after hydrolysis of irradiated BSA/sulfanilamide mixtures. This was demonstrated by autoradiography of paper chromatograms. The same compound was also detected in an irradiated [35S]cystine non‐labelled sulfanilamide mixture. It was not detected, however, after irradiation of a mixture of all amino acids of BSA excluding cystine. These data suggest that cystine residues are involved in the photobinding of sulfanilamide (or its photo

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1986.tb03561.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

Abstract—Escherichia coliwas transformed with a pUC 19 plasmid which contained a 4,5′,8‐trimethylpsoralen cross‐link specifically at position T410‐A411, and transformants in which the cross‐link had been repaired were scored on the basis of ampicillin resistance. Repair was only seen after induction of the SOS‐system by shortwave ultraviolet irradiation. The repair efficiency was 6%, and of 100 colonies analyzed only two was found to be mutated at the cross‐linked site: a T‐A transversion was observed at position 410. A repair mechanism which does not involve recombin

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1986.tb03562.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

Abstract—A broad‐band UVA source that emits primarily350–400 nm radiation and no measurable radiation below 340 nm was used to test toxicity and mutagenicity at the thymidine kinase locus in L5178Y, subclone 3.7.2C (TK+/‐) mouse lymphoma cells. Cells were exposed to a fluence of 0 to 80 × 104J/m2. The relationship between UVA fluence and survival was found to have a shoulder region followed by an exponential decrease in survival at higher fluence levels. An exposure‐dependent increase in mutation was observed with increasing fluences from 0 to about 60 × 104J/m2. An approximately 3‐ to 4‐fold increase in mutations (trifluorothymidine resistance) over unexposed, control cells was seen at a fluence that resulted in 90% cell killing. We conclude that UVA radiation is a mutagen in the L5178Y mouse lymphoma cells use

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1986.tb03563.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

Abstract—When DNA is complexed with Cu2+ions it becomes sensitized to mid‐UV light. Irradiation of the complex at 310 ± 10 nm produces marked changes in absorption and circular dichroism spectra in addition to those in melting profiles of irradiated samples. These variations show conformational changes in DNA structure due to a photoreduction of some copper sites in the DNA‐Cu2+complex. In addition to this effect an irreversible damage in DNA structure could be invoked to explain the observed behaviour. These facts can be related to the presence in DNA‐Cu2+complex of a small absorption band extending up to mid‐UV range while the absorption of DNA is negligible in this spec

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1986.tb03564.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY