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PubMed1979

Recognition of structure of 5-halogenated derivatives of ara-UTP by DNA polymerase gamma and reverse transcriptase.

This report deals with the test of a series of 5-halogenated derivatives of ara-UTP for the inhibition of DNA polymerase gamma and viral reverse transcriptase. The compounds newly synthesized and tested were; ara5-FUTP, ara5-C1UTP, ara5-BrUTP and ara5-IUTP. The results were: 1) All these compounds were inhibitory to DNA polymerase gamma and reverse transcriptase. The mode of inhibitions was, in all cases, competitive against dTTP. 2) Ki values for these inhibitors with DNA polymerase gamma were lower than those with reverse transcriptase. 3) Ara5-ClUTP was less inhibitory to reverse transcriptase than other derivatives.

Animals↗
PubMed1998

[Mutagenicity of mixtures of halogenated aliphatic hydrocarbons and polycyclic aromatic hydrocarbons in the Ames test with TA98 and TA100].

Within the framework of the assessment of the genotoxic potential of environment samples the Salmonella-microsome-test (Ames-test) is often used as a screening-test. It is one of the most applied biotest systems and possesses a large scientific acceptance. Because most environment samples are mixtures of various substances, possible effects resulting from the combination should be taken into account with regard to the mutagenic potential. In this context we investigated eight polycyclic aromatic hydrocarbons each combined with six halogenated aliphatic hydrocarbons as to their mutagenicity in the Salmonella-microsome-test with TA98 and TA100. For an exogenous metabolizing system, Arochlor 1254 induced rat liver S9-mix was used. Benz-a-pyrene in combination with bromodichloromethane (Ames neg. in TA98 and TA100 +S9) showed an increase in the number of the revertants up to 25% in TA98 and TA100 (+S9). Carbon tetrachloride (Ames neg. in TA98 and TA100 +S9) showed in TA100 (+S9) an increase in the number of the revertants of 18% at most. In the combination 3-methylcholanthrene with dichloromethane the number of revertants in TA98 (+S9) increased by 25% and in TA100 (+S9) by 18%. Hexachloroethane (weakly mutagenic in TA98 +S9) in combination showed in TA98 (+S9) a slightly increased number of revertants with benz-a-pyrene as well with 3-methylcholanthrene. All the other substances tested (chrysene, phenanthrene, anthanthrene, dibenz-a, i-pyrene, triphenylene, fluoranthene) in combination with either tetrachloroethylene or trichloroethene did not cause an increase in mutagenicity.

Animals↗
PubMedDate not supplied

Improvement of poult performance following Bordetella avium challenge by administration of a novel oxy-halogen formulation.

The ability of a novel oxy-halogen formulation (OHF) to alter the development of bordetellosis (turkey coryza) in large white turkey poults was assessed. Bordetella avium (BA)-infected (1-day-of-age) and noninfected control poults received 0, 0.008%, or 0.016% of an OHF continuously in the drinking water. At 4, 7, 10, 14, and 17 days of age, reisolation of BA from infected poults was attempted. Infected poults receiving 0.016% OHF exhibited significantly lower cumulative BA reisolation rates (90%) when compared with infected poults receiving 0 (96.7%) or 0.008% OHF (100%). At 7, 14, and 17 days of age, infected poults in the OHF-treated groups were significantly heavier than those BA-challenged poults receiving control water. Feed utilization was significantly improved from hatch to 7 days of age in BA-infected poults receiving OHF when compared with infected poults receiving control water. Clinical symptoms were severe only in untreated, infected poults and were mild or absent in all others. Damage to the tracheal epithelium, as measured by scanning electron microscopy, paralleled the clinical signs. Tracheal epithelial damage was virtually eliminated by OHF administration in infected poults. These results suggest that OHF treatment ameliorates many of the symptoms frequently associated with bordetellosis in young turkeys.

Administration, Oral↗
PubMed1999

Maternal and developmental toxicity of halogenated 4'-nitrodiphenyl ethers in mice.

In an ongoing effort to delineate structure-activity relationships in the developmental toxicity of diphenyl ethers, we evaluated the maternal and developmental toxicity of 10 diphenyl ethers related to the herbicide nitrofen. All possible trichlorophenyl 4'-nitrophenyl ethers were evaluated, as were the 2,4-difluorophenyl and 2,4-dibromophenyl 4'-nitrophenyl ethers. We also evaluated bifenox and chlomethoxyfen, which are 2,4-dichlorophenyl congeners with meta-substituents on the 4'-nitrophenyl ring. Nitrofen (2,4-dichlorophenyl 4'-nitrophenyl ether) was included for comparison. Identity of the halogen affected the postnatal (but not prenatal) mortality induced by 2,4-dihalogenated 4'-nitrophenyl ethers. The presence of 3'-substituents on the 4'-nitrophenyl ring reduced both pre- and postnatal toxicity of 2,4-dichlorinated congeners. Among chlorinated 4'-nitrophenyl congeners without meta-substituents on the nitrophenyl ring, the position of chlorine substituents strongly affected the congener's potential for inducing prenatal vs. postnatal syndromes. All congeners increased liver to body weight ratios in unmated females, but such increases were not well-correlated with either prenatal or postnatal embryotoxicity.

Animals↗
PubMed2000

Frozen shell approximation violation in negative ion formation from halogenated benzenes via dissociative attachment

A series of benzene derivatives (R(1)C(6)H(4)R(2)) has been studied by means of electron capture negative ion mass spectrometry (ECNI-MS), and PM3 quantum chemical calculations. The dissociation channel M(-.) --> Hal(-) + (M - Hal). is analysed from the point of view of symmetry conservation. Generally, a symmetry ban on dissociation may be avoided in at least two ways: (i) out-of-plane vibrations of the halogen atom in the molecular negative ion (MNI), mixing pi- and sigma-states of the anion; (ii) symmetrical in-plane vibration of the C-Hal bond, changing the order of the empty levels in the MNI with subsequent radiationless conversion into a sigma-state. Our analysis shows that neither of them provides a satisfactory explanation of the ECNI mass spectra for chlorobenzene, if one retains the usual assumption that an additional electron goes into the LUMO of the neutral molecule. Thus, it may be concluded that in this case electron capture causes a significant perturbation of the energy ordering of vacant orbitals, thus making the frozen shell approximation inapplicable. Copyright 2000 John Wiley & Sons, Ltd.

Journal Article↗
PubMed2000

Competitive behavior in the interactive toxicology of halogenated aromatic compounds.

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that binds and mediates responses to many halogenated aromatic compounds (HACs). Exposure to mixtures of HACs frequently results in nonadditive behavior in both in vivo and in vitro assays. One cause is antagonism, which results when two or more ligands compete for a limited supply of the AhR; one interacts agonistically to induce a strong response, and the other interacts unproductively, eliciting little or no response. This study involves the mechanism by which HACs induce CYP 1A1. Agonistic (e.g., TCDD) and unproductive (e.g., PCB 153) HACs behaved similarly through the stages of initial AhR binding and conversion of the initial AhR-ligand complex to the form that possesses increased affinity for the bound ligand. They diverged in the ability of the AhR-HAC complex to bind to a synthetic oligonucleotide containing the consensus dioxin response enhancer sequence, as studied by the gel retardation assay. Competition for the Ah receptor was used to explain antagonistic behavior between TCDD and other HACs in both the gel retardation assay and the downstream response of CYP 1A1 induction in primary rat hepatocytes.

Animals↗
PubMed2001

Syntheses of halogenated ethenyl isocyanide chromium complexes as organometallic precursor molecules for ethenyl and ethynyl isocyanides.

The radical alkylation of tetraethylammonium pentacarbonyl(cyano)chromate 1 yielded the halogenated ethyl isocyanide complexes [(CO)5Cr(CN-CClX-CClYF)] 3 (a, X= Cl, Y= F; b, X = F, Y= F and c, X=Y= Cl). Dehalogenation of 3 using zinc in diethyl ether gave [(CO)5Cr(CN-CX=CFY)] 4. The compounds 4a, b reacted with various nucleophiles exclusively at the difluoromethylene group. The unstable phosphorane 5, which is formed on reaction of 4b with trimethylphosphane, decomposed thermally and on hydrolysis yielding pentacarbonyl(1,2-difluoroethenyl isocyanide)chromium (6). The cyano substituent can be introduced in the beta position of the isocyanide function by reaction of 4a, b with potassium cyanide, leading to the formation of [(CO)5Cr(CN-CX=CF-CN)] (7). Reactions of 4a, b with organolithium or organomagnesium compounds yielded [(CO)5Cr(CN-CX=CF-R)] (8) and [(CO)5Cr(CN-CF=CF-C...C-CF=CF-NC)Cr(CO)5] (10). The trimethylsilyl group in 8a, b, d could be removed by a solution of potassium carbonate in methanol leading to [(CO)5Cr(CN-CX=CF-Cn-H)] (11) (n=2,4). Octacarbonyldicobalt reacted with 8e under coordination of the C-C triple bond to the hexacarbonyldicobalt fragment, resulting in the cluster compound 12. The crystal and molecular structure of 8i, 11 a, b, and 12 were elucidated by X-ray crystallography. The alkenyl and alkynyl isocyanides CN-CCl=CF2 (13a), CN-CF=CF2 (13b), CN-CCl=CClF (13c), CN-CF=CFH (14), CN-CC-H (15), CN-CC-CN (16), and CN-CCl=CF-CN (17) were obtained by flash vacuum pyrolysis of 4a, 4b, 4c, 6, and 7a, respectively.

Journal Article↗
PubMed2003

Highly functionalized organomagnesium reagents prepared through halogen-metal exchange.

Organomagnesium reagents occupy a central position in synthetic organic and organometallic chemistry. Recently, the halogen-magnesium exchange has considerably extended the range of functionalized Grignard reagents available for synthetic purposes. Functional groups such as esters, nitriles, iodides, imines, or even nitro groups can be present in a wide range of aromatic and heterocyclic organomagnesium reagents. Also various highly functionalized alkenyl magnesium species can be prepared. These recent developments as well as new applications of organomagnesium reagents in cross-coupling reactions and amination reactions will be covered in this Review.

Journal Article↗
PubMed2005

Reciprocal mutations in TM2/TM3 in a D2 dopamine receptor background confirms the importance of this microdomain as a selective determinant of para-halogenated 1,4-disubstituted aromatic piperazines.

We recently demonstrated that in the D4 dopamine receptor the aromatic microdomain that spans the interface of the second and third transmembrane (TM) domains influences the high affinity interactions of extremely D4-selective ligands possessing a 1,4-disubstituted aromatic piperazine/piperidine (1,4-DAP) structure. On the basis of their substructural features and patterns of sensitivity to mutations constructed in a D4 receptor background, the D4-selective 1,4-DAPs were categorized as having two distinct modes of binding that we named mode-1 and mode-3 [1]. Here we extend these findings of the ligand-receptor structure-affinity relationships for some of these highly D4-selective 1,4-DAPs by measuring the effect of the corresponding reciprocal TM2/TM3 mutations constructed in a D2 dopamine receptor background on the binding affinity of the para-halogenated mode-1 ligands L750,667 and FAUC213. The results indicate that the D2-V2.61F + FV3.28-3.29LM mutant binds L750,667 and FAUC213 with significantly increased affinity, i.e., its binding profile becomes more D4-like. These findings further support the assignment of the TM2/TM3 aromatic microdomain encompassing positions 2.61 and 3.28-3.29 as a 1,4-DAP D4-selectivity microdomain and highlights the importance of the precise emplacement of aromatics in this microdomain as key to the selective molecular recognition of L750,667 and FAUC213.

Animals↗
PubMed2004

Group 1 coordination chains and hexagonal networks of host cyclotriveratrylene with halogenated monocarbaborane anions.

Halogenated carbaborane ions [CB(11)H(6)X(6)](-) in which X=Cl or Br have been combined with the host molecule cyclotriveratrylene (CTV) and Group 1 metal cations to give crystalline materials. The complexes [Na(ctv)(H(2)O)(CB(11)H(6)X(6))](CF(3)CH(2)OH) feature chiral Na-CTV coordination chains with complexation of the [CB(11)H(6)X(6)](-) ion by the Na(+) ion, together with the CTV molecular cavity. The coordination chains are hydrogen bonded together to give a puckered two-dimensional hexagonal grid structure. [K(ctv)(CB(11)H(6)Cl(6))(CF(3)CH(2)OH)(0.5)] is essentially isostructural. Complexes [Rb(ctv)(CB(11)H(6)Br(6))(H(2)O)] and [Cs(ctv)(CB(11)H(6)X(6))(CH(3)CN)] are coordination polymers with related distorted hexagonal grid structures. Use of N,N'-dimethylformamide (DMF) as a solvent results in an entirely different type of assembly, with [Na(2)(dmf)(4)(H(2)O)(2)(ctv)][(dmf)(0.5)(ctv)][CB(11)H(6)Br(6)](2) showing unusual [Na-mu-(dmf)-Na] bridges, and once again forming a distorted hexagonal coordination polymer.

Journal Article↗
PubMed2005

Hydrocarbon oxidation by beta-halogenated dioxoruthenium(VI) porphyrin complexes: effect of reduction potential (RuVI/V) and C-H bond-dissociation energy on rate constants.

beta-Halogenated dioxoruthenium(VI) porphyrin complexes [Ru(VI)(F(28)-tpp)O(2)] [F(28)-tpp=2,3,7,8,12,13, 17,18-octafluoro-5,10,15,20-tetrakis(pentafluorophenyl)porphyrinato(2-)] and [Ru(VI)(beta-Br(8)-tmp)O(2)] [beta-Br(8)-tmp=2,3,7,8,12,13,17,18-octabromo-5,10,15,20- tetrakis(2,4,6-trimethylphenyl)porphyrinato(2-)] were prepared from reactions of [Ru(II)(por)(CO)] [por=porphyrinato(2-)] with m-chloroperoxybenzoic acid in CH(2)Cl(2). Reactions of [Ru(VI)(por)O(2)] with excess PPh(3) in CH(2)Cl(2) gave [Ru(II)(F(20)-tpp)(PPh(3))(2)] [F(20)-tpp=5,10,15,20-tetrakis(pentafluorophenyl)porphyrinato(2-)] and [Ru(II)(F(28)-tpp)(PPh(3))(2)]. The structures of [Ru(II)(por)(CO)(H(2)O)] and [Ru(II)(por)(PPh(3))(2)] (por=F(20)-tpp, F(28)-tpp) were determined by X-ray crystallography, revealing the effect of beta-fluorination of the porphyrin ligand on the coordination of axial ligands to ruthenium atom. The X-ray crystal structure of [Ru(VI)(F(20)-tpp)O(2)] shows a Ru=O bond length of 1.718(3) A. Electrochemical reduction of [Ru(VI)(por)O(2)] (Ru(VI) to Ru(V)) is irreversible or quasi-reversible, with the E(p,c)(Ru(VI/V)) spanning -0.31 to -1.15 V versus Cp(2)Fe(+/0). Kinetic studies were performed for the reactions of various [Ru(VI)(por)O(2)], including [Ru(VI)(F(28)-tpp)O(2)] and [Ru(VI)(beta-Br(8)-tmp)O(2)], with para-substituted styrenes p-X-C(6)H(4)CH=CH(2) (X=H, F, Cl, Me, MeO), cis- and trans-beta-methylstyrene, cyclohexene, norbornene, ethylbenzene, cumene, 9,10-dihydroanthracene, xanthene, and fluorene. The second-order rate constants (k(2)) obtained for the hydrocarbon oxidations by [Ru(VI)(F(28)-tpp)O(2)] are up to 28-fold larger than by [Ru(VI)(F(20)-tpp)O(2)]. Dual-parameter Hammett correlation implies that the styrene oxidation by [Ru(VI)(F(28)-tpp)O(2)] should involve rate-limiting generation of a benzylic radical intermediate, and the spin delocalization effect is more important than the polar effect. The k(2) values for the oxidation of styrene and ethylbenzene by [Ru(VI)(por)O(2)] increase with E(p,c)(Ru(VI/V)), and there is a linear correlation between log k(2) and E(p,c)(Ru(VI/V)). The small slope (approximately 2 V(-1)) of the log k(2) versus E(p,c)(Ru(VI/V)) plot suggests that the extent of charge transfer is small in the rate-determining step of the hydrocarbon oxidations. The rate constants correlate well with the C-H bond dissociation energies, in favor of a hydrogen-atom abstraction mechanism.

Crystallography, X-Ray↗
PubMed1983

6-Halogen derivatives of 2-(3-benzoylphenyl)propionic acid.

The synthesis of the 6-fluoro (I a), 6-chloro (I b) and 6-bromo (I c) derivatives of the known antiinflammatory agent 2-(3-benzoylphenyl)propionic acid (ketoprofen) is reported. The procedure employed involves the direct phase-transfer methylation of the appropriate arylacetonitriles and the subsequent hydrolysis of the alpha-methyl arylacetonitriles (V) thus obtained. It is noteworthy that (V b) and (V c) were not accompanied by alpha, alpha-dimethylated contaminants, owing to the steric hindrance of the chloro and bromine substituent. The pharmacological evaluation of (I a-c) showed that the presence of the halogen unexpectedly abolished the antiinflammatory and antipyretic activities of the model drug. The 6-ethoxy derivative (I d), isolated as by-product of the synthesis of (I a) was also found inactive. A hypothesis has been formulated on the loss of activity of these compounds.

Animals↗
PubMed1992

Halogenated analogues of tamoxifen: synthesis, receptor assay, and inhibition of MCF7 cells.

This study was conducted to develop a ligand for imaging estrogen-receptor-positive breast tumors by positron emission tomography or single photon emission computed tomography. We synthesized fluoro and iodo analogues of tamoxifen, and these halogenated analogues produced greater affinity for binding to the receptor than tamoxifen. Values of the inhibition affinity constants were as follows: tamoxifen, 15,000 nM; fluoromethyl-N,N-diethyltamoxifen, 2500 nM for the cis isomer and 500 nM for the trans isomer; and iodomethyl-N,N-diethyltamoxifen, 1500 nM for the cis isomer and 1000 nM for the trans isomer. In studies of human MCF7 breast tumor cell growth, concentrations that inhibited tumor growth in 50% of the cases were as follows: tamoxifen, 11 microM; fluoromethyl-N,N-diethyltamoxifen, 4.5 and 11.8 microM for the cis and trans isomers, respectively; and iodomethyl-N,N-diethyltamoxifen, 2.4 and 6.3 microM for the cis and trans isomers, respectively. These studies suggest that both fluoro and iodo analogues of tamoxifen may be useful diagnostic compounds for predicting the response of estrogen-receptor-positive breast tumors to tamoxifen analogues used in chemotherapy.

Animals↗
PubMed1994

Synthesis of C(10)-halogenated prostaglandins.

The synthesis of halogenated prostaglandins at position C(10), starting from prostaglandin A2, has been accomplished, as well as an efficient regioselective hydroxylation of the upper chain of the prostanoid structure. Evaluation of the inhibitory effects on the proliferation of the K-562 cell line in vitro is presented. When the prostaglandin was modified in the upper chain, the antimitotic activity for bromo derivatives 4b, c and iodo derivative 5b had shown substantial improvements in their activities according to their ID50 values (28, 25, and 22 micrograms/mL, respectively). Attention is called to the significance of chloro derivative 3a in terms of its high potency, determined by its ID50 value (0.06 micrograms/mL).

Acetylation↗
PubMed2002

Application of sulfur as a matrix for laser desorption/ionization in the characterization of halogenated fullerenes.

The application of sulfur as a matrix for matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) analysis of highly chlorinated and fluorinated fullerenes is reported. Control over fluorofullerene fragmentation which resulted in the domination of the molecular peak C(60)F(36)(-) was achieved, with the optimal matrix-to-analyte ratio found to be 1000:1. We suggest the possible mechanism of the molecular ion formation according to the charge transfer between the sulfur anions and C(60)F(36). For the first time the LDI and MALDI mass spectra of the highly chlorinated fullerene C(60)Cl(x)(x(max) approximately 32) are presented. The formation of odd chlorine ions (positive and negative) is observed. We conclude that use of sulfur as a matrix leads to a significant decrease in fragmentation of the halogenated fullerenes.

Journal Article↗
PubMed2003

Inhibition of CYP 1A2-dependent MROD activity in rat liver microsomes: an explanation of the hepatic sequestration of a limited subset of halogenated aromatic hydrocarbons.

Many classes of halogenated aromatic compounds (HACs) are highly lipophilic environmental contaminants that exert toxic effects via the Ah receptor signal transduction pathway and whose metabolism generally involves monooxygenase enzymes of the CYP 1A family. Despite their lipophilicity, a high proportion of the body burden of certain polychlorinated dibenzo-p-dioxins and coplanar polychlorinated biphenyls is sequestered in liver, a process believed to involve CYP 1A2. In this work we examined HAC-induced inhibition of the demethylation of 7-methoxyresorufin, a process that is selectively catalyzed by CYP 1A2. 2,3,7,8-Tetrachlorodibenzo-p-dioxin, 3,3',4,4'-tetrachlorobiphenyl (PCB 77) and 3,3',4,4',5-pentachlorobiphenyl (PCB 126) were found to be strong competitive inhibitors of methoxyresorufin-O-demethylase activity, consistent with the high ability of hepatic tissue to sequester these compounds selectively.

Animals↗
PubMed2004

Interaction between halogenated aromatic compounds in the Ah receptor signal transduction pathway.

Many toxic and biochemical responses to halogenated aromatic compounds (HACs) such as polychlorinated biphenyls (PCBs) and polychlorinated dibenzo-p-dioxins (PCDDs) are mediated through the aryl hydrocarbon receptor (AhR), which is an intracellular cytosolic target for HACs. Environmental exposure to HACs almost always involves complex mixtures of congeners, some of which can antagonize the action of potent HACs such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). In this work we studied TCDD and representative PCB congeners, alone and in mixture, for their effect on CYP1A gene transcription and protein levels in primary rat hepatocytes. Together with our previous work, our results suggest that formation of the Ah receptor-ligand-DRE (dioxin response element) complex is the principal point of divergence in the mechanism between an AhR agonist and an AhR antagonist. The coplanar PCBs 77 and 126 and the mono-ortho PCB 156 were full agonists toward CYP1A1 gene transcription and CYP1A protein levels, showing typical additive behavior with TCDD to the target molecule AhR. In contrast, the nonplanar PCB 153 antagonized the action of TCDD, even at concentrations that occupied a significant fraction of AhR molecules. Competitive inhibition explains the commonly reported decrease of ethoxyresorufin-O-deethylase (EROD) activity when PCBs are present in high concentrations and the antagonism of PCBs to the EROD activity of TCDD. The result is that Western blotting offers a much more reliable measure of CYP1A protein concentration than does the EROD assay, despite the greater convenience of the latter.

Animals↗
PubMed2001

Possible molecular targets of halogenated aromatic hydrocarbons in neuronal cells.

Halogenated aromatic hydrocarbon including polychlorinated biphenyls (PCBs) are persistent and bioaccumulative environmental toxicants. Although health effects associated with exposure to these chemicals, including motor dysfunction and impairment in memory and learning, have been identified, their molecular site of action is unknown. Previous study from this laboratory demonstrated that, while ortho PCBs perturbed intracellular signaling mechanisms including Ca2+ homeostasis, receptor-mediated inositol phosphate production and translocation of PKC, non-ortho PCBs did not. Since PKC signaling pathway is implicated in the modulation of motor behavior, as well as learning and memory, and the roles of PKC are isoform-specific, we have now studied the effects of two structurally distinct PCBs on isoforms of PKC in cerebellar granule cell culture model. Cells were exposed to 2,2'-dichlorobiphenyl (ortho PCB; 2,2'-DCB) or 4,4'-dichlorobiphenyl (non-ortho PCB; 4,4'-DCB) for 15 min, respectively, and subsequently fractionated and immunoblotted against the selected PKC monoclonal antibodies (alpha, gamma, delta, epsilon, lambda, iota). While 2,2'-DCB induced a translocation of PKC-alpha [cytosol (% control): 54 +/- 12 at 25 microM and 66 +/- 10 at 50 microM; membrane (% control): 186 +/- 37 at 25 microM and 200 +/- 48 at 50 microM] and -epsilon [cytosol (% control): 92 +/- 12 at 25 microM and 97 +/- 15 at 50 microM; membrane (% control): 143 +/- 23 at 25 microM and 192 +/- 24 at 50 microM] from cytosol to membrane fraction in a concentration-dependent manner, 4,4'-DCB had no effects. 2,2'-DCB induced translocation of PKC-alpha was blocked by pretreatment with sphingosine, suggesting a possible role of sphingolipid pathway. Although reports on implication of PKC-gamma with learning and memory are relatively extensive, the expression of this particular isoform in the primary cerebellar granule cells was below the detectable level. PKC-delta, -lambda and -iota were present in these cells, but were not altered by PCB exposure. These results suggest that the effects of 2,2'-DCB on PKC is isoform-dependent and PKC-alpha as well as PKC-epsilon may be target molecules for ortho-PCBs in neuronal cells.

Animals↗