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PubMed2004

Synthesis of [11C]/(13C)amines via carbonylation followed by reductive amination.

Twelve 11C-labelled amines were prepared via 11C-carbonylation followed by reductive amination. The 11C-carbonylation was performed in the presence of tetrakis(triphenylphosphine)palladium using aryl iodides or aryl triflates, [11C]carbon monoxide and phenyl-/methylboronic acid. The [11C]ketones formed in this step were then transformed directly into amines by reductive amination using different amines in the presence of TiCl4 and NaBH3CN. The 11C-labelled amines were obtained with decay-corrected radiochemical yields in the range 2-78%. The radiochemical purity of the isolated products exceeded 98%. (13C)Benzhydryl-phenyl-amine was synthesised and analysed by NMR spectroscopy for confirmation of the labelling position. Specific radioactivity was determined for the same compound. The reference compounds were prepared by reductive amination of ketones using conventional reaction conditions and three of the compounds were novel. The presented approach is a new method for the synthesis of [11C]/(13C)amines.

Journal Article↗
PubMed1994

Detection and identification of side reactions of halogenated hydrocarbon solvents with amines of pharmaceutical interest by secondary processes to the neutralizations of sulphonphthaleinic dyes with these amines.

The neutralization reactions between amines and diprotic acid dyes in organic solvents generate (dye-, amineH+) and [dye2-, (amineH+)2] ion associates that show two absorption bands in the visible spectrum. An unidentified third absorption band; which appears with a high amine concentration, proves that halogenated hydrocarbon solvents (dichloromethane, chloroform, 1,2-dichloroethane, and carbon tetrachloride) give side reactions with amines (atropine, tropine, quinine, ephedrine, and ajmaline) that generate a quaternary ammonium salt, N-halogenalkylammonium halide ([N(+)-RX,X-]). The molecular weight of the quaternary ammonium salt is the sum of the amine and that of the solvent. The (N(+)-RX,X-) ion associated reacts with [dye2-, (amineH+)2] by substitution reactions, forming (dye2-, amineH+, N(+)-RX) and (dye2-, (N(+)-RX)2] ion associates that justify the third absorption band. The amine-solvent side reactions are of first order with respect to the amine, being very slow processes with rate constant values from 399.4 h-1 (tropine-dichloromethane reaction) to 15.8 h-1 (atropine-1,2- dichloroethane reaction). Rate constants increase with the basicity of the amine measured in the halogenated hydrocarbons employed. Rate constants also increase with a reduction in the number of the halogen atoms present in the halogenated solvent. The new visible absorption band that appears in the amine-dye neutralization gives a quick colorimetric test to bring to light this kind of side reaction in these solvents.

Amines↗
PubMed1998

A Cobalt(III) Chiroporphyrin and Its Amine Adducts. A Potential Chiral NMR Shift Reagent for Amines.

The chlorocobalt(III) complex of alphabetaalphabeta-tetramethylchiroporphyrin, CoCl(TMCP), has been prepared as a potential enantioselective host or chiral NMR shift reagent for optically active amines. The X-ray structure of CoCl(OHCH(2)CH(3))(TMCP) shows the six-coordinate cobalt(III) ion at the center of a strongly ruffled porphyrin. The 2-fold-disordered ethanol ligand interacts with the chiroporphyrin host by two C-H.O hydrogen bonds to the carbonyl groups of two ester substituents. Primary amines bind to this diamagnetic cobalt(III) center to form cationic 2:1 complexes in which the (1)H NMR resonances of the axial ligands are shifted upfield of tetramethylsilane by the porphyrin ring current. Coordinated enantiopure 2-alkylamines exhibit NMR signals for the protons of the amine group which are characteristic of their (R or S) absolute configuration. The bis-complexes of the same amines in racemic form exist as three different species, (R,R), (S,S), and (R,S), in 1:1:2 relative ratios. Negligible enantioselection by the chiral host suggests kinetic control of bis(amine) complex formation on cobalt(III). The X-ray structure of the bis((S)-2-butylamine) complex [Co((S)-NH(2)CH(CH(3))CH(2)CH(3))(2)(TMCP)][CoCl(4)](0.5) shows a 2-fold-disordered amine on one face of the porphyrin only. The unique amine on the other face is held within the porphyrin groove by a network of weak interactions including N-H.O and C-H.O hydrogen bonds. With its ability to induce good resolution of axial ligand (1)H NMR resonances and slow dissociation kinetics of its bis-adducts, CoCl(TMCP) may be useful as a chiral NMR shift reagent for conformational studies of chiral amines and as an analytical reagent for the determination of their enantiomer composition.

Journal Article↗
PubMed2006

Rhodium, palladium and platinum complexes of tris(pyridylalkyl)amine and tris(benzimidazolylmethyl)amine N4-tripodal ligands.

To investigate the influence of a potentially N4-tripodal amine ligand on the structure and internal exchange processes of its complexes with late transition metals, five rhodium, six palladium and two platinum complexes have been prepared from seven alkyl-bridged N-heterocyclic amine tripodal ligands: tris(2-pyridylmethyl)amine, (2-(2-pyridylethyl))bis(2-pyridylmethyl)amine, bis(2-(2-pyridylethyl))-2-pyridylmethylamine, bis(2-(2-pyridylethyl))amine, ((6-(hydroxymethyl)-2-pyridyl)methyl)bis(2-pyridylmethyl)amine, tris(2-benzimidazolylmethyl)amine (tbima) and tris(3-ethyl-2-benzimidazolylmethyl)amine. Single-crystal X-ray diffraction studies were completed for ten complexes: the d6-rhodium(III) complexes are octahedral with kappa 4 N-bound ligands, whereas the d8-palladium(II) and d8-platinum(II) complexes are square planar, kappa 3 N-bound by the tripodal ligand with a dangling N-donor leg, except for the unusual [Pd2(tbima)2Cl2]Cl2 dimer in which each palladium(II) ion is square planar and bound by two benzimidazole legs from one tbima ligand, one leg from the other tbima ligand and a chloride ancillary ligand. Cation bilayers are a common structural motif in the crystal structures. Variable-temperature 1H NMR studies reveal exchange occurs between the coordinated and dangling N-donor legs in the palladium and platinum complexes. Exchange free energy (Delta G++ c) values have been calculated and some general rules governing the favoured complex structures and exchange pathways elucidated. The palladium(II) and platinum(II) complexes of a ligand with an pyridylethyl leg are unstable with respect to elimination of vinylpyridine.

Journal Article↗
PubMed2006

Mechanism-based cofactor derivatization of a copper amine oxidase by a branched primary amine recruits the oxidase activity of the enzyme to turn inactivator into substrate.

The copper amine oxidases (CAOs) have evolved to catalyze oxidative deamination of unbranchedprimary amines to aldehydes. We report that a branched primary amine bearing an aromatization-prone moiety, ethyl 4-amino-4,5-dihydrothiophene-2-carboxylate (1), is recognized enantioselectively (S >> R) by bovine plasma amine oxidase (BPAO) both as a temporary inactivator and as a substrate. Substrate activity results from an O(2)-dependent turnover of the covalently modified enzyme, with release of 4-aminothiophene-2-carboxylate (2) as ultimate product. Interaction of (S)-1 with BPAO occurs within the enzyme active site with a dissociation constant of 0.76 microM. Evidence from kinetic and spectroscopic studies, and HPLC analysis of stoichiometric reactions of BPAO with (S)-1, combined with a model study using a quinone cofactor mimic, establishes that the enzyme metabolizes 1 according to a transamination mechanism. Following the initial isomerization of substrate Schiff base to product Schiff base, a facile aromatization of the latter results in a metastable N-aryl derivative of the reduced cofactor aminoresorcinol, which is catalytically inactive. The latter derivative is then slowly oxidized by O(2), apparently facilitated partially by the active-site Cu(II), to form a quinonimine of the native cofactor that releases 2 upon hydrolysis or transimination with substrate amine. Preferential metabolism of (S)-1 is consistent with the preferential removal of the pro-Salpha-proton in metabolism of benzylamine by BPAO. This study represents the first report of product identification in metabolism of a branched primary amine by a copper amine oxidase and suggests a novel type of reversible mechanism-based (covalent) inhibition where inhibition lifetime can be fine-tuned independently of inhibition potency.

Amine Oxidase (Copper-Containing)↗
PubMed1991

Uptake of N-(4'-pyridoxyl)amines and release of amines by renal cells: a model for transporter-enhanced delivery of bioactive compounds.

The importing of vitamin B6 by renal proximal tubular cells from the rat is facilitated and Na(+)-dependent and reflects specificity for the meta-phenolate pyridinium structure with a 5-hydroxymethyl function. This transporter can, however, accept competitively each of the natural nonphosphorylated vitamers (pyridoxine, pyridoxamine, and pyridoxal) and other B6 analogues differing only in the groups at position 4. A series of N-(4'-pyridoxyl)amines was synthesized by sodium borohydride or boro[3H]hydride reduction of aldimines formed by condensing the amines with pyridoxal. The unlabeled B6-secondary amine compounds were found to competitively inhibit the uptake of [4'-3H]pyridoxine by the renal cells. Moreover, the 3H-labeled N-(4'-pyridoxyl)amines were shown to enter the cells by the process facilitated by the B6 transporter. Upon entry the labeled compounds were converted to N-(5'-phospho-4'-pyridoxyl)amines in a reaction catalyzed by pyridoxal kinase, an enzyme that tolerates considerable functional variation in position 4 of the B6 structure. The 5'-phosphates were subsequently converted within the cell to pyridoxal 5'-phosphate with liberation of the original amine in a reaction catalyzed by pyridoxamine (pyridoxine) 5'-phosphate oxidase, an enzyme with broad specificity for 4'-substituted amines on the 5'-phospho-B6 structure. This system illustrates how knowledge of transporter specificity can permit design of a compound with potential biologic activity. A drug or other intracellular effector may be piggybacked onto a transported solute (e.g., vitamin or other nutrient) that gains facilitated entry to a cell and is, thereafter, metabolized to release the active compound.

Amines↗
PubMed1993

Biogenic amines in silage. 1. The occurrence of biogenic amines in silage.

In laboratory silages made from orchardgrass, red clover and oats, significant levels of toxic biogenic amines were found. The most widespread were putrescine and cadaverine, concentrations of spermidine, spermine and histamine were ten times lower on average. Of the amines considered, putrescine content seems to be the most sensitive indicator of the extent of putrefaction in silages. A relationship between the putrescine contents and the degree of proteolysis was found. The biogenic amine content is closely connected with both the variety of crop ensiled and even more so with the method and the efficiency of preservation. Neither the application of formic acid nor wilting suppressed the formation of any of the amines in silages selectively. Formic acid suppressed the total concentration of amines to 23% as compared with controls. The highest levels of amines were found in orchardgrass and oat silages; smaller amounts were detected in clover silages. In the case of very poorly preserved silage 100-150 g of toxic amines can be consumed by a cow in a day. This could have a deleterious effect on the physiological condition and the performance of livestock.

Animals↗
PubMed2005

Distribution of amines in water/AOT/n-hexane reverse micelles: influence of the amine chemical structure.

The distribution of different aliphatic and aromatic amines: n-butylamine (n-BA), isobutylamine (i-BA), tert-butylamine (t-BA), piperidine (PIP), N,N-dimethylaniline (DMA) and N-methylaniline (MA) in water/sodium 1,4-bis(2-ethylhexyl)sulfosuccinate(AOT)/n-hexane reverse micelles was investigated by steady-state fluorescence measurements. The partition constants were measured by an indirect method based on the effect that amine partitioning exert on the bimolecular rate of the reaction between a microphase incorporated fluorophore (Ru(bpy)2+(3)) and the quencher, (Fe(CN)3-(6)). For MA, that can act as a quencher of the fluorophore a direct method was used. The results show that primary amines have larger partition constants than the secondary ones. For tertiary amines the distribution constants were practically negligible. Laser flash photolysis experiments confirmed that tertiary amines, both aliphatic and aromatic, are not incorporated to the micellar pseudophase. The effect of the amine structure on the partition constant was analyzed through linear solvation free energy relationships (LSER) using solute parameters and compared with those obtained for alcohols. Hydrogen bond interactions with the AOT polar heads appear to be the main driving force for the distribution of amines between the organic and micellar pseudophases, whereas the size of the alkyl or aromatic group tends to hinder it.

Journal Article↗
PubMed2004

Mechanism of helix induction on a stereoregular Poly((4-carboxyphenyl)acetylene) with chiral amines and memory of the macromolecular helicity assisted by interaction with achiral amines.

Cis-transoidal poly((4-carboxyphenyl)acetylene) (poly-1) is an optically inactive polymer but forms an induced one-handed helical structure upon complexation with optically active amines such as (R)-(1-(1-naphthyl)ethyl)amine ((R)-2) in DMSO. The complexes show a characteristic induced circular dichroism (ICD) in the UV-visible region of the polymer backbone. Moreover, the macromolecular helicity of poly-1 induced by (R)-2 can be "memorized" even after complete replacement of (R)-2 by various achiral amines. We now report fully detailed studies on the mechanism of the helicity induction and memory of the helical chirality of poly-1 by means of UV-visible, CD, and infrared spectroscopies. We have found that a one-handed helix is cooperatively induced on poly-1 upon the ion pair formation of the carboxy groups of poly-1 with optically active amines and that the bulkiness of the chiral amines plays a crucial role for inducing an excess of a single-handed helix. On the other hand, the free ion formation was found to be essential for the macromolecular helicity memory of poly-1 after the replacement of the chiral amine by achiral amines, since the intramolecular electrostatic repulsion between the neighboring carboxylate ions of poly-1 significantly contributes to reduce the atropisomerization process of poly-1. On the basis of the mechanism of helicity induction and the memory of the helical chirality drawn from the present studies, we succeeded in creating an almost perfect memory of the induced macromolecular helicity of poly-1 with (R)-2 by using 2-aminoethanol as an achiral chaperoning molecule to assist in maintaining the memory of helical chirality.

Journal Article↗
PubMed2004

Effect of amine nature on reaction rate and mechanism in nucleophilic substitution reactions of 2,4-dinitrophenyl X-substituted benzenesulfonates with alicyclic secondary amines.

Second-order rate constants have been measured for reactions of 2,4-dinitrophenyl X-substituted benzenesulfonates with a series of alicyclic secondary amines. The reaction proceeds through S-O and C-O bond fission pathways competitively. The S-O bond fission occurs more dominantly as the amine basicity increases and the substituent X in the sulfonyl moiety becomes more strongly electron withdrawing, indicating that the regioselectivity is governed by the amine basicity as well as the electronic nature of the substituent X. The S-O bond fission proceeds through an addition intermediate with a change in the rate-determining step at pK(a) degrees = 9.1. The secondary amines are more reactive than primary amines of similar basicity for the S-O bond fission. The k(1) value has been determined to be larger for reactions with secondary amines than with primary amines of similar basicity, which fully accounts for their higher reactivity. The second-order rate constants for the S-O bond fission result in linear Yukawa-Tsuno plots while those for the C-O bond fission exhibit poor correlation with the electronic nature of the substituent X. The distance effect and the nature of reaction mechanism have been suggested to be responsible for the poor correlation for the C-O bond fission pathway.

Journal Article↗
PubMed1996

Reductive Amination of Aldehydes and Ketones with Sodium Triacetoxyborohydride. Studies on Direct and Indirect Reductive Amination Procedures(1).

Sodium triacetoxyborohydride is presented as a general reducing agent for the reductive amination of aldehydes and ketones. Procedures for using this mild and selective reagent have been developed for a wide variety of substrates. The scope of the reaction includes aliphatic acyclic and cyclic ketones, aliphatic and aromatic aldehydes, and primary and secondary amines including a variety of weakly basic and nonbasic amines. Limitations include reactions with aromatic and unsaturated ketones and some sterically hindered ketones and amines. 1,2-Dichloroethane (DCE) is the preferred reaction solvent, but reactions can also be carried out in tetrahydrofuran (THF) and occasionally in acetonitrile. Acetic acid may be used as catalyst with ketone reactions, but it is generally not needed with aldehydes. The procedure is carried out effectively in the presence of acid sensitive functional groups such as acetals and ketals; it can also be carried out in the presence of reducible functional groups such as C-C multiple bonds and cyano and nitro groups. Reactions are generally faster in DCE than in THF, and in both solvents, reactions are faster in the presence of AcOH. In comparison with other reductive amination procedures such as NaBH(3)CN/MeOH, borane-pyridine, and catalytic hydrogenation, NaBH(OAc)(3) gave consistently higher yields and fewer side products. In the reductive amination of some aldehydes with primary amines where dialkylation is a problem we adopted a stepwise procedure involving imine formation in MeOH followed by reduction with NaBH(4).

Journal Article↗
PubMed1986

Photochemical linking of primary aromatic amines to carrier proteins to elicit antibody response against the amine haptens.

Two chemical methods, diazocoupling and reaction with isocyanates, are commonly used to conjugate primary aromatic amines with carrier proteins in order to elicit antibody responses against the aromatic amine haptenic group. Limitations of these conjugation techniques include the requirement for specific functional groups on the carrier protein which generally limits the degree of haptenic substitution obtainable, the many possible side reactions yielding hapten-hapten and carrier-carrier conjugates which waste valuable materials and lower desired hapten-carrier conjugate yields, and, in some cases, conjugation conditions which may denature the carrier protein (e.g., alkaline coupling conditions). We report here a photolabeling approach for conjugating primary aromatic amines to carrier proteins which avoids some of the problems of other conjugation methods and which was used to elicit antibodies against the primary aromatic amine hapten. The method described here is of general application for coupling primary aromatic amines to the carrier proteins and circumvents many of the problems inherent in the isocyanate or diazocoupling methods. 3-Azido-N-ethylcarbazole (ANEC), the azido analog of 3-amino-N-ethylcarbazole, was conjugated to bovine serum albumin (BSA), human transferrin (TR), thyroglobulin (TH), poly-(lysine X tyrosine), and poly-(lysine X phenylalanine) using standard photolabeling procedures. After photolysis, the conjugated proteins or polypeptides were separated from the unbound products of ANEC photolysis on a Sephadex G-10 column. The conjugated proteins were extracted with isobutanol which demonstrated that approximately 20% of the ANEC was covalently coupled to the protein carriers and that the larger portion of the aromatic haptens was non-covalently and hydrophobically bound to the carriers. The ANEC-protein conjugates used for immunization demonstrated a total covalently and non-covalently bound ANEC epitope density of 90 per BSA, 107 per TR and 800 per TH molecule. Rabbits were immunized with the three conjugated proteins and the production of antibody specific for the 3-amino-N-ethylcarbazole hapten was demonstrated by enzyme-linked immunosorbent assay and by inhibition studies using hapten-carrier conjugates of free hapten. The results demonstrate that antibodies against aromatic amine haptens may be raised by immunizing animals with hapten-carrier protein conjugates produced by photolabeling. Since the coupling conditions are very mild and the functional group requirements are so general (requiring only the presence of C-H, N-H, C = O, C = S, or S-H bonds) most carrier proteins should be suitable for use in this method.(ABSTRACT TRUNCATED AT 400 WORDS)

Affinity Labels↗
PubMed2003

Non-amine-based dopamine transporter (reuptake) inhibitors retain properties of amine-based progenitors.

Without exception, therapeutic and addictive drugs that produce their primary effects by blocking monoamine transporters in brain contain an amine nitrogen in their structure. This fundamental canon of drug design was based on a prevailing premise that an amine nitrogen is required to mimic the structures of monoamine neurotransmitters and other natural products. Non-amines, a novel class of compounds that contain no amine nitrogen, block monoamine transporters in the nM range and display markedly high selectivity for monoamine transporters, but not for receptors. Non-amines retain the spectrum of biochemical and pharmacological properties characteristic of amine-bearing counterparts. These novel drugs compel a revision of current concepts of drug-monoamine transporter complex formation and open avenues for discovery of a new generation of therapeutic drugs.

Animals↗
PubMed2001

Synthesis and characterisation of N-glycosyl amines from the reaction between 4,6-O-benzylidene-D-glucopyranose and substituted aromatic amines and also between 2-(o-aminophenyl)benzimidazole and pentoses or hexoses.

Twelve N-glycosyl amines were synthesised using 4,6-O-benzylidene-D-glucopyranose and different substituted aromatic amines, including some diamines that resulted in bis-glycosyl amines. Another set of six N-glycosyl amines was synthesised using different hexoses and pentoses and 2-(o-aminophenyl)benzimidazole. All compounds were isolated as solid products and purified, their elemental compositions were established, and these were characterised by NMR (1H and 13C), UV-Vis, and FTIR spectroscopy, by FAB mass spectrometry (molecular-ion peaks gave molecular weights), and by their optical rotations. While the protected saccharide, 4,6-O-benzylidene-D-glucopyranose, exists as a mixture of beta and alpha anomers in solution, the corresponding N-glycosyl amines were of only the beta anomeric form as determined by NMR and FTIR spectroscopy. On the other hand, N-glycosyl amines synthesised from 2-(o-aminophenyl)benzimidazole prefer the alpha anomeric form, and in two cases a mixture of both the beta and the alpha anomers were observed. The trends observed in the chemical shifts were compared among different products.

Amines↗
PubMed1993

Exposure of beta H-crystallin to hydroxyl radicals enhances the transglutaminase-susceptibility of its existing amine-donor and amine-acceptor sites.

beta H-crystallin was exposed to radiolytically generated hydroxyl radicals at defined radical concentrations, and its capacity to act as an amine-acceptor substrate and as an amine-donor substrate for transglutaminase were investigated. [14C]Methylamine was used as a probe for labelling amine-acceptor sites; a novel biotinylated hexapeptide was used to label amine-donor sites. The results demonstrate that both primary amine incorporation and hexapeptide incorporation by transglutaminase are considerably increased after oxidative attack on the crystallin. The identity of the labelled subunits was established, and it is shown that, in both cases, this increased incorporation is not due to the production of new substrates, but that the existing incorporation sites become more susceptible. Moreover, using the newly developed probe, we could identify, for the first time, the major crystallin subunits active as amine-donor substrates (both before and after treatment) to be beta B1-, beta A3- and beta A4-crystallin. These data support the proposal that oxidative stress and transglutaminase activity may be jointly involved in the changes found in lens crystallins with age and in the development of cataract.

Amines↗
PubMed1993

Biogenic amines in silage. 2. The dynamics of the formation of biogenic amines in silage.

When analysing a series of laboratory silages made from orchardgrass, red clover and oats, the fluctuating dynamics of biogenic amines were observed. For levels of putrescine and cadaverine, a rapid exponential increase culminating approximately 30-50 days after ensiling is typical. A small decrease, reaching the minimum at approximately the 100th day, is sometimes followed by a second increase in amine concentrations achieving its maximum approximately 200-230 days after ensiling. Irregular curves of the dynamics probably originate in the simultaneous decarboxylation and deamination reactions along with other relevant amine degradation processes. The dynamics of other biogenic amines-spermidine, spermine and histamine are more difficult to predict. The changes in histamine levels resembled those in the diamines. Some 200 days after ensiling, considerable increases in this toxic amine were observed. The dynamics of some quality criteria, especially the degree of proteolysis, were in many cases similar to those of the amines.

Animals↗
PubMed1984

Cation exchange--a common mechanism in the storage and release of biogenic amines stored in granules (vesicles)? II. Comparative studies on sodium-induced release of biogenic amines from the synthetic weak cation-exchangers Amberlite IRC-50 and duolite CS-100 and from biogenic (granule-enriched) materials.

Superfusion of phenylethylamine-, noradrenaline- or histamine-charged weak (carboxyl) cation-exchangers (IRC-50 and Duolite CS-100) with isotonic NaCl caused a release of the amines. Similarly, bovine chromaffin granules and nerve granule preparations from bovine splenic nerve, rat vas deferens and rat corpus striatum released their amine(s) upon superfusion with the same solution. The courses of release from the synthetic and biogenic materials showed very similar characteristics and fitted the same exchange equations. The observations support the view that the matrices of the biogenic amine-storing granules have the properties of weak cation-exchanger materials with carboxyls as the cation-binding groups, and that the NaCl-induced release of the biogenic amines is due to cation exchange (Na+ in equilibrium Amine+). The possibility that amine release in vivo is based on cation exchange is discussed.

Adrenergic Fibers↗
PubMed1995

[Chemical carcinogenesis and cytochrome P450: carcinogenic aromatic amine-induced P450 and hepatocarcinogenic susceptibility to the aromatic amine in the rodent].

The N-hydroxyl and/or N-acetoxy derivatives of carcinogenic 4-aminoazo dyes, which were thought to be proximate and ultimate metabolites, were synthesized in our laboratory in 1975, and their chemical and biological characteristics were further examined. The results strongly supported the hypothesis that the metabolic conversions, N-hydroxylation and its O-acylation, of carcinogenic aromatic amines are important processes for their carcinogenicity. Carcinogenic aromatic amines such as heterocyclic aromatic amines and aminoazo dyes induced predominantly cytochrome P450IA2 (CYP1A2), which is responsible for the mutagenic activation and N-hydroxylation of the amines in the rodent. The induction rate and total activity of this enzyme were well correlated with sex, species, and target organ differences in hepatocarcinogenic susceptibility of animals to the aromatic amines. During hepatocarcinogenic process with an aromatic amine, the expression and induction of CYP1A2 decreased especially in preneoplastic liver cells as judged by the expression of a placental form of glutathione S-transferase.

Amines↗