Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Aziridines”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources
PubMed2002

Metalloporphyrin-mediated asymmetric nitrogen-atom transfer to hydrocarbons: aziridination of alkenes and amidation of saturated C-H bonds catalyzed by chiral ruthenium and manganese porphyrins.

Chiral metalloporphyrins [Mn(Por*)(OH)(MeOH)] (1) and [Ru(Por*)(CO)(EtOH)] (2) catalyze asymmetric aziridination of aromatic alkenes and asymmetric amidation of benzylic hydrocarbons to give moderate enantiomeric excesses. The mass balance in these nitrogen-atom-transfer processes has been examined. With PhI=NTs as the nitrogen source, the aziridination of styrenes, trans-stilbene, 2-vinylnaphthalene, indene, and 2,2-dimethylchromene catalyzed by complex 1 or 2 resulted in up to 99 % substrate conversions and up to 94 % aziridine selectivities, whereas the amidation of ethylbenzenes, indan, tetralin, 1-, and 2-ethylnaphthalene catalyzed by complex 2 led to substrate conversions of up to 32 % and amide selectivities of up to 91 %. Complex 1 or 2 can also catalyze the asymmetric amidation of 4-methoxyethylbenzene, tetralin, and 2-ethylnaphthalene with "PhI(OAc)(2) + NH(2)SO(2)Me", affording the N-substituted methanesulfonamides in up to 56 % ee with substrate conversions of up to 34 % and amide selectivities of up to 92 %. Extension of the "complex 1 + PhI=NTs" or "complex 1 + PhI(OAc)(2) + NH(2)R (R=Ts, Ns)" amidation protocol to a steroid resulted in diastereoselective amidation of cholesteryl acetate at the allylic C-H bonds at C-7 with substrate conversions of up to 49 % and amide selectivities of up to 90 % (alpha:beta ratio: up to 4.2:1). An aziridination- and amidation-active chiral bis(tosylimido)ruthenium(VI) porphyrin, [Ru(Por*)(NTs)(2)] (3), and a ruthenium porphyrin aziridine adduct, [Ru(Por*)(CO)(TsAz)] (4, TsAz=N-tosyl-2- (4-chlorophenyl)aziridine), have been isolated from the reaction of 2 with PhI=NTs and N-tosyl-2-(4-chlorophenyl)aziridine, respectively. The imidoruthenium porphyrin 3 could be an active species in the aziridination or amidation catalyzed by complex 2 described above. The second-order rate constants for the reactions of 3 with styrenes, 2-vinylnaphthalene, indene, ethylbenzenes, and 2-ethylnaphthalene range from 3.7-42.5x10(-3) dm(3) mol(-1) s(-1). An X-ray structure determination of complex 4 reveals an O- rather than N-coordination of the aziridine axial ligand. The fact that the N-tosylaziridine in 4 does not adopt an N-coordination mode disfavors a concerted pathway in the aziridination by a tosylimido ruthenium porphyrin active species.

Alkenes↗
PubMed2026

Unveiling Aziridine-Containing Natural Products by Genomic and Spectroscopic Approaches.

Aziridine-containing natural products are prized for their potent bioactivities, yet their scarcity and poorly understood biosynthesis have limited systematic exploration. Here, we address this by integrating genome mining with a 1H-13C coupled HSQC metabolomic approach that exploits the distinctive NMR signatures of aziridines, enabling their direct detection from complex extracts. This strategy unveiled the desertolides, the first macrolides incorporating a rare terminal 2-methyl-aziridine-2-carboxylate moiety. Genetic and isotopic studies identified a dedicated biosynthetic subcluster (desA-desN) that assembles and installs this unit from glutamate, and heterologous expression confirmed the self-sufficiency of this subcluster. Direct MS evidence reveals the aziridine moiety covalently bound to the active-site Cys113 of DesN, establishing this KAS III homolog as the first dedicated aziridine-transferase and a promising tool for polyketide engineering. Bioinformatic analysis uncovered over 50 biosynthetic gene clusters, suggesting that this aziridine-associated biosynthetic logic may be more widespread than currently appreciated. This work establishes a tractable platform for the targeted discovery and engineered biosynthesis of aziridine-containing natural products, opening this underexplored pharmacophore to systematic interrogation.

Aziridines↗
PubMed2005

Radical cations of phenyl-substituted aziridines: what are the conditions for ring opening?

Radical cations were generated from different phenyl-substituted aziridines by pulse radiolysis in aqueous solution containing TlOH.+, N3. or SO4.- as oxidants or in n-butyl chloride, by 60Co gamma radiolysis in Freon matrices at 77 K, and in some cases by flash photolysis in aqueous solution. Depending on the substitution pattern of the aziridines, two different types of radical cations are formed: if the N atom carries a phenyl ring, the aziridine appears to retain its structure after oxidation and the resulting radical cation shows an intense band at 440-480 nm, similar to that of the radical cation of dimethylaniline. Conversely, if the N atom carries an alkyl substituent while a phenyl ring is attached to a C-atom of the aziridine, oxidation results in spontaneous ring opening to yield azomethine ylide radical cations which have broad absorptions in the 500-800 nm range. In aqueous solution the two types of radical cations are quenched by O2 with different rates, whereas in n-butyl chloride, the ring-closed aziridine radical cations are not quenchable by O2. The results of quantum chemical calculations confirm the assignment of these species and allow to rationalize the different effects that phenyl rings have if they are attached in different positions of aziridines. In the pulse radiolysis experiments in aqueous solution, the primary oxidants can also be observed, whereas in n-butyl chloride a transient at 325 nm remains unidentified. In the laser flash experiments, both types of radical cations were also observed.

Aziridines↗
PubMed2006

Rational design of aziridine-containing cysteine protease inhibitors with improved potency: studies on inhibition mechanism.

To enable a rational design of improved cysteine protease inhibitors, the present work investigates trends in the inhibition potency of aziridine derivatives with a substituted nitrogen center. To predict the influence of electron-withdrawing substituents, quantum chemical computations of the ring opening of N-formylated, N-methylated, and N-unsubstituted aziridines with thiolate were performed. They revealed that the N-formyl group leads to a strong decrease of the reaction barrier and a considerable increase in exothermicity due to stabilization of the transition state. In contrast, a nucleophilic attack at the carbonyl carbon atom is characterized by very low reaction barriers, suggesting a reversible reaction, thus providing the theoretical background for the reversible inhibition of cysteine proteases by peptidyl aldehydes. Reactions of aziridine building blocks (diethyl aziridine-2,3-dicarboxylate 1, diethyl 1-formyl aziridine-2,3-dicarboxylate 2) with a model thiolate in aqueous solution which were followed by NMR spectroscopy and mass spectrometry, showed the N-formylated compound 2 to readily undergo a ring-opening reaction. In contrast, the reaction of 1 with the thiolate is much slower. Enzyme assays with the cysteine protease cathepsin L showed 2 to be a 5000-fold better enzyme inhibitor than 1. Dialysis assays clearly proved irreversible inhibition. These experiments, together with the results obtained with the model thiolate, indicate that the main inhibition mechanism of the N-formylated aziridine 2 is the ring-opening reaction rather than the reversible attack of the active site cysteine residue at the carbonyl carbon atom.

Aziridines↗
PubMed1995

Aziridine analogs of [[trans-(epoxysuccinyl)-L-leucyl]amino]-4-guanidinobutane (E-64) as inhibitors of cysteine proteases.

Aziridine derivatives of E-64 have been synthesized, and their characterization against the cysteine proteases cathepsin B, cathepsin L, and papain is reported. The inhibition was found to be strongly pH-dependent, with maximum activity observed at pH 4, indicating that the protonated aziridinium ion form of the inhibitor is the more reactive form. At low pH, the peptide aziridine HO-(L)Az-Leu-NH-iAm inactivated papain with a second-order rate constant, kinac/Ki, of 7.0 x 10(4) M-1 s-1, a value very close to that observed with E-64 or with the corresponding epoxysuccinyl analog HO-(L)Eps-Leu-NH-iAm. This demonstrates that with the correct peptide sequence, aziridine analogs of E-64 can be good irreversible inhibitors of cysteine proteases. Substitution of the epoxysuccinyl moiety by an aziridine does not affect the specificity of inhibition against the three proteases used in this study. The D-diastereomer is the preferred (by 10-fold) diastereomer for the inhibition of cysteine proteases. The reactivity of both diastereomers of iBuNH-Az-LeuPro-OH against cathepsin B was also found to be much lower than that of iBuNH-(L)Eps-LeuPro-OH, which is a potent selective inhibitor of cathepsin B. These differences are attributed mainly to the presence of the protonated aziridine ring, which can modify the binding mode of aziridine analogs at the active site of cysteine proteases.

Animals↗
PubMed1999

New peptidic cysteine protease inhibitors derived from the electrophilic alpha-amino acid aziridine-2,3-dicarboxylic acid.

Three different types of peptides containing aziridine-2, 3-dicarboxylic acid (Azi) as an electrophilic alpha-amino acid at different positions within the peptide chain (type I, N-acylated aziridines with Azi as C-terminal amino acid; type II, N-unsubstituted aziridines with Azi as N-terminal amino acid; type III, N-acylated bispeptidyl derivatives of Azi) have been synthesized and tested as inhibitors of the cysteine proteases papain, cathepsins B, L, and H, and calpains I and II, as well as against several serine proteases, one aspartate, and one metalloprotease. All aziridinyl peptides are specific cysteine protease inhibitors. Papain and cathepsins B and L are inhibited irreversibly, whereas cathepsin H and calpains are inhibited in a non-time-dependent manner. Some compounds turned out to be substrates for serine proteases and for the metalloprotease thermolysin. Remarkable differences can be observed between the three different types of inhibitors concerning stereospecificity, pH dependency of inhibition, selectivity between different cysteine proteases, and the importance of a free carboxylic acid function at the aziridine ring for inhibition. Above all type II inhibitors, aza analogues of the well-known epoxysuccinyl peptides, are potent cysteine protease inhibitors. With the exception of BOC-Leu-Gly-(S, S+R,R)-Azi-(OEt)2 (28a+b), a highly selective and potent cathepsin L inhibitor, N-acylated aziridines of type I are weaker inhibitors than type II or type III compounds. The observed results can be explained by different binding modes of the three types of inhibitors with respect to their orientation in the S- and S'-binding sites of the enzymes. Furthermore, the presence of a protonated aziridine N modifies the binding mode of type II inhibitors.

Aziridines↗
PubMed2004

Rhodium(II)-catalyzed aziridination of allyl-substituted sulfonamides and carbamates.

Several unsaturated sulfonamides underwent intramolecular aziridination when treated with PhI(OAc)(2), MgO, and catalytic Rh(2)(OAc)(4) to give bicyclic aziridines in excellent yield. Treatment of the resulting azabicyclic sulfonamides in methanol in the presence of p-TsOH resulted in exclusive opening of the aziridine ring at the most substituted position affording six- and seven-membered ring products in high yield. In contrast, the intramolecular aziridination of several cycloalkenyl-substituted carbamates did not require a Rh(II) catalyst and proceeded via an iminoiodinane intermediate. The resulting tricyclic aziridines underwent ring opening when treated with various nucleophiles to give anti-derived products as expected for nucleophilic attack at the three-membered ring. The iodine(III)-mediated reaction of a 3-indolyl-substituted carbamate, however, required a Rh(II) catalyst. The expected aziridine was not observed, but rather simultaneous spirocyclization of C(3) and stereoselective syn-acylation at C(2) occurred to give compound 41, whose structure was unequivocally established by an X-ray crystallographic study. The reaction proceeds in a stepwise manner via a metal-free zwitterionic intermediate which is attacked by a nucleophilic reagent on the same side of the amide anion. Related reactions occurred with both a 2-indolyl- and 3-benzofuranyl-substituted carbamate but with lower stereoselectivity.

Aziridines↗
PubMed2005

Selective ring-opening of nonactivated amino aziridines by thiols and unusual nucleophilic substitution of a dibenzylamino group.

[Reaction: see text]. The reaction of chiral 2-(1-aminoalkyl)aziridines 1 with different thiols, in the presence of BF3*Et2O, is reported. The obtained products were dependent on the structure of the starting amino aziridines 1. Thus, enantiopure (2S,3S)-2-(alkylthio)alkane-1,3-diamines 2 were obtained from aziridines with C-2 substituents with lower steric congestion and partially racemized (2S,3S)-2,3-bis(alkylthio)alkan-1-amines 3 (ee = 56-66%) from aziridines with larger C-2 subtituents. In both cases, the opening of the nonactivated aziridine ring at C-2 took place with retention of configuration and proceeded with regio- and stereoselectivity at C-2. In the synthesis of 3, 2 equiv of thiol reacts with 1 and the opening of aziridine ring at C-2 was followed by an unusual displacement of the dibenzylamino group by a second equivalent of thiol. The regiochemistry and relative configuration of compounds 3 was established by single-crystal X-ray analysis. A mechanism is proposed to explain the results obtained.

Amines↗
PubMedDate not supplied

Alkylation of DNA with aziridine produced during the hydrolysis of N,N',N''-triethylenethiophosphoramide.

A reaction pathway by which thiotepa (N,N',N''-triethylenethiophosphoramide) and tepa (N,N',N''-triethylenethiophosphoramide), its major metabolite in humans, alkylate and depurinate DNA involves hydrolysis to aziridine (ethylene imine), a highly reactive monofunctional alkylating agent. Hydrolytic cleavage of an N-P bond of thiotepa releases aziridine which reacts with DNA, resulting in depurination and formation of the stable N-7 adduct 7-(2-aminoethyl)guanine and an aminoethyl adduct of adenine. Chromatographically identical alkylated products were observed in the reaction of thiotepa and tepa with individual nucleosides. Adducts with deoxycytidine or thymidine were not detected. Aziridine was measured by HPLC after derivatization with 1,2-naphthoquinone 4-sulfate. On the basis of the identity of the DNA adducts and the rate of formation of aziridine by hydrolysis in vitro, thiotepa is concluded to be a lipophilic, stabilized form of aziridine which serves as a cell-penetrating carrier of aziridine.

Alkylating Agents↗
PubMed1985

Dermatitis from aziridine hardener in printing ink.

13 of 51 workers developed dermatitis of the hands and face after handling a water-based ink containing a polyfunctional aziridine hardening agent. Improper work practices resulted in skin contamination with the ink and its ingredients. The aziridine hardener contained trimethylolpropane triacrylate (TMPTA). The incidence of dermatitis was highest among the ink mixers who handled the undiluted aziridine (6 of 8 workers affected), was lower among printers who handled ink containing 2 to 4% aziridine (7 of 22 workers affected), and was absent in workers who did not handle ink. The mean latency from first contact with the ink to the development of the rash was 3.2 months among the ink mixers, and 6.2 months among the printers. The present findings demonstrate the risk of handling aziridine hardeners when protective clothing is not properly used and when work practices result in direct skin contact. Further research should be performed to discern whether aziridine compounds themselves, free of TMPTA, can cause dermatitis.

Acrylates↗
PubMed2006

Advances in nitrogen transfer reactions involving aziridines.

In recent years, our search for new nitrogen transfer reactions has concentrated on aziridine chemistry. This Account highlights our efforts toward the synthesis and functionalization of aziridines. In the course of our research, we have investigated the electrochemical aziridination of olefins, the acid-catalyzed ring opening of aziridines, and the development of transition metal mediated nitrogen allylation, arylation, and alkenylation of unprotected aziridines. Our studies have also involved the synthesis of aziridine-based enamine intermediates and their stereoselective transformations into heterocyclic compounds.

Journal Article↗
PubMed1988

Comparative DNA damage induced by nitroimidazole-aziridine drugs: 1. Effects of methyl substitution on drug action.

RSU-1069 (1-(-3-aziridinyl-2-hydroxypropyl)-2-nitroimidazole) is a bifunctional chemo- and radiosensitizing agent. The properties of these functional groups may be examined by comparison of drug-induced DNA damage oxically, a measure of aziridine-induced damage and, during anoxic electrochemical reduction of the nitro-group, a measure of DNA damage resulting from the combined activity of reduced nitro group intermediates and alkylation by the aziridine moiety. In this study, a series of nitroimidazole aziridines have been studied and compared. The compounds used were RSU-1069, five methyl substituted derivatives: RSU-1131, RSU-1150, RSU-1164, RSU-1172, RB-7040; a 4-nitroimidazole derivative, RSU-1170, and RSU-1137, the non-alkylating hydrolysis product of RSU-1069. DNA damage, occurring oxically or as a consequence of nitro reduction, decreases with increasing substitution of the aziridine ring. Most DNA damage occurring oxically is produced by RSU-1069 and RSU-1170, both compounds having unsubstituted aziridine rings; least DNA damage is produced by RSU-1137. In general, the extent of DNA damage during electrochemical reduction is greater than that occurring oxically, this being due to an assumed combination of alkylation and reduced nitro-group intermediates. There is a direct correlation between the half-lives of the compounds and the extent of DNA damage occurring under oxic conditions. A direct correlation of the aerobic toxicities of the compounds tested, relative to RSU-1069, and the number of unsubstituted sites available for nucleophilic attack on the aziridine moiety has also been shown.

Coliphages↗
PubMed1993

Identification, synthesis and properties of 5-(aziridin-1-yl)-2-nitro-4-nitrosobenzamide, a novel DNA crosslinking agent derived from CB1954.

5-(Aziridin-1-yl)-4-hydroxylamino-2-nitrobenzamide, the active form of 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB1954), can react spontaneously with oxygen, and in aqueous solution yields 5-(aziridin-1-yl)-2-nitro-4-nitrosobenzamide and hydrogen peroxide. Mild biological reducing agents such as NAD(P)H, reduced thiols and ascorbic acid rapidly re-reduced the nitroso compound to the hydroxylamine. Both compounds were equally efficient at inducing cytotoxicity and DNA interstrand crosslinking in cells when exposed in phosphate-buffered saline (PBS). Neither agent was capable of inducing cross-links in isolated DNA. When acetyl coenzyme A was included in the incubation, crosslink formation was seen with the hydroxylamine, but not with the nitroso compound. Thus, the nitroso compound is acting as a prodrug for the hydroxylamine, and needs to be reduced to this compound to exert its cytotoxic effects. In vivo anti-tumour tests showed that neither compound was effective in its own right. This may be due to the rapid reduction of the nitroso to the hydroxylamine, and the reaction of the hydroxylamine with serum proteins. The chemical synthesis of the 5-(aziridin-1-yl)-2-nitro-4-nitrosobenzamide, and an improved synthesis of 5-(aziridin-1-yl)-4-hydroxylamino-2-nitrobenzamide is described. These results emphasize the potential efficacy of the in situ activation of prodrugs such as CB1954 either by endogenous enzymes such as DT diaphorase, or by antibody directed enzyme prodrug therapy (ADEPT).

Animals↗
PubMed1977

The interaction of 1-(2(diarylmethoxy)ethyl)aziridines with histamine receptors in the longitudinal muscle strip of the guinea pig ileum.

The time course of the onset and decline of histamine antagonism by 1-(2-(diarylmethoxy)ethyl)aziridines, compounds which could be expected to have H1-receptor alkylating properties, was investigated on the longitudinal muscle strip of the guinea pig ileum. Experiments were performed with normal preparations and with muscle strips pretreated with a prostaglandin synthesis inhibitor in order to prevent spontaneous rise of muscle tone. In contrast to the previously reported observation that antihistaminic potency decreased with prolongation of the preincubation time, histamine antagonism by the aziridine compounds remained at a constant level for more than 60 min in the presence of indomethacin. This indicated that the aziridines are not hydrolyzed either directly in solution or after interaction with the tissue since the supposed hydrolysis product had a significantly lower antihistaminic activity. A comparison between 1-(2-diphenylmethoxy)ethyl)aziridine and diphenhydramine showed the former compound to have a slightly more rapid onset and a considerably more rapid decline of histamine receptor blockade. It was concluded that 1-(2-(diarylmethoxy)ethyl)aziridines did not alkylate the histamine H1-receptor in the longitudinal muscle layer of the guinea pig ileum.

Animals↗
PubMed1987

Estrogenic affinity labels: synthesis, irreversible receptor binding, and bioactivity of aziridine-substituted hexestrol derivatives.

To develop an affinity label for the estrogen receptor that would be an estrogen agonist, rather than antagonist, we prepared several aziridine derivatives of the potent nonsteroidal estrogen hexestrol [3R,4S)-3,4-bis(4-hydroxyphenyl)hexane) bearing an aziridine function on the side chain. Three functional groups link the hexestrol ligand and the aziridine: a carbonyl group (ketone or ester), a thioether, or a methylene chain. The apparent competitive binding affinity of these derivatives for the estrogen receptor ranges from 1.8% to 25% that of estradiol, and most of them bind in a time-dependent, irreversible manner with the receptor, although the rate and efficiency of this binding vary widely, often with relatively small changes in structure. This is consistent with the irreversible attachment requiring a precise alignment of activating and reacting residues in the binding site of the receptor. The estrogenic and antiestrogenic activity of these aziridine derivatives was investigated in MCF-7 human breast cancer cells. Most of the compounds are agonists, with one being an antagonist. The derivative (6R,7S)-1-N-aziridinyl-6,7-bis(4-hydroxyphenyl)-5-nonanone (keto-nonestrol aziridine 3) appears to have the most ideal behavior of the estrogenic affinity labeling agents prepared: It is an agonist, and it binds to receptor irreversibly, efficiently, and quite rapidly.

Affinity Labels↗
PubMed2003

Effect of nitroreduction on the alkylating reactivity and cytotoxicity of the 2,4-dinitrobenzamide-5-aziridine CB 1954 and the corresponding nitrogen mustard SN 23862: distinct mechanisms of bioreductive activation.

The dinitrobenzamide aziridine CB 1954 (1) and its nitrogen mustard analogue SN 23862 (6) are prodrugs that are activated by enzymatic nitroreduction in tumors. Bioactivation of 1 is considered to be due to reduction of its 4-nitro group to the hydroxylamine and subsequent formation of the N-acetoxy derivative; this acts as a reactive center, in concert with the aziridine moiety, to provide a bifunctional DNA cross-linking agent (Knox model). It is currently unclear whether bioactivation of 6 occurs by the same mechanism or results from the electronic effects of nitroreduction on reactivity of the nitrogen mustard moiety. To discriminate between these mechanisms, we have synthesized the hydroxylamine and amine derivatives of 1 and 6, plus related compounds, and determined their alkylating reactivities in aqueous solution, using LC/MS to identify reaction pathways. The relationships between substituent electronic effects, reactivity, and cytotoxicity were determined using the UV4 cell line, which is defective in nucleotide excision repair (thus avoiding differences in repair kinetics). Alkylating reactivity correlated with the electron-donating character of the ortho or para substituent in the case of the mustards, with a less marked electronic effect for the aziridines. Importantly, there was a highly significant linear relationship between cytotoxic potency and alkylating reactivity in both the aziridine and the mustard series, with the notable exception of 4, the 4-hydroxylamine of 1, which was 300-fold more toxic than predicted by this relationship. This demonstrates that the high potency of 4 does not result from activation of the aziridine ring, supporting the Knox model. The single-step bioactivation of 6, to amino or hydroxylamine metabolites with similar potency to 4, is a potential advantage in the use of dinitrobenzamide mustards as prodrugs for activation by nitroreductases.

Aniline Mustard↗
PubMed2002

Aziridines: epoxides' ugly cousins?

Aziridines, the nitrogenous analogues of epoxides, have until recently excited far less interest amongst synthetic organic chemists than their oxygenated counterparts, with some justification. A range of reviews concerned with the physical properties, synthesis (asymmetric and otherwise), reactions and utility of aziridines exists; this review briefly summarizes the similarities and differences between oxiranes and their nitrogenated analogues, concentrating on the underlying properties of aziridines and recent developments in their chemistry. In addition to descriptions of the physical nature of aziridines, especially those features which underpin their utility as synthetic intermediates, the sections beneath describe reactions involving alkylative ring-opening and synthesis of aziridines.

Alkylating Agents↗
PubMed1996

Reduction of the toxicity and mutagenicity of aziridine in mammalian cells harboring the Escherichia coli fpg gene.

Aziridine (ethyleneimine) reacts with DNA in vitro, mainly at the N7 position of guanine and N3 of adenine, then imidazole ring opening of the modified guanine results in formation of formamidopyrimidine (FaPy) residues. The Escherichia coli fpg gene encodes a DNA glycosylase that removes FaPy residues from DNA. To determine whether aziridine produces FaPy lesions in mammalian cells we have expressed the E.coli fpg gene in CHO cells. The transfected cells, expressing high levels of the bacterial protein, are more resistant to the toxic and mutagenic effects of aziridine than the control population. Less DNA damage was measured by quantitative PCR analysis in transfected than in control cells treated with equimolar concentrations of aziridine. The results suggest that aziridine produces in vivo FaPy residues that could account for the deleterious effects of this compound.

Animals↗