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[Research on a new side-chain liquid crystalline polysiloxane as stationary phase for capillary column gas chromatography].

A new stationary phase, side-chain liquid crystalline polysiloxane, was obtained and used in capillary column gas chromatography. Two kinds of side-chain polysiloxane, PSI5 and PSI6, were characterized by polarized light microscopy (POM), differential scanning calorimetry (DSC) and X-ray diffraction and proved to be smectic phase Sc. Two fused-silica capillary columns (0.25 mm i.d.) were coated with 5 g/L solutions of PSI5 and PSI6 in dichloromethane by the static method, named column 15 and column 16. Numbers of theoretical plate were 1,598/m-2,423/m (I5) and 3,191/m-4,235/m (I6) for anthracene at 200 degrees C-240 degrees C. These columns showed wide operation temperature range (I5: 50 degrees C-200 degrees C; I6: 100 degrees C-260 degrees C), outstanding thermostability and weak polarity. These columns exhibited unique selectivity for many organic compounds, especially positional isomers. For example, the mixtures of anthracene, phenanthrene and fluorene were well separated on column I5 and I6; dimethyl benzene isomers were well separated on column I5, but they were not separated on column I6; dimethyl phenol isomers were well separated on column I5, but they were not wholly separated on column I6. The different selectivities of these columns are mainly due to the different chemical structures.

Calorimetry, Differential Scanning↗

[Selectivity tuning in multi-binary eluents for reversed-phase liquid chromatography (RPLC)].

In this article, the retention equation and the relationship between retention parameters and the parameters of molecular structure deduced from statistical thermodynamics in RPLC have been used to explain the difference of selectivity towards a particular species of compounds polycyclic aromatic hydrocarbons (PAHs). Methanol/water, acetonitrile/water and isopropanol/acetonitrile have been provided in advance, then the retention behaviors of sixteen PAHs under three binary solvent systems have been investigated. It is found that each pair of binary solvents of methanol/water, acetonitrile/water and isopropanol/acetonitrile has its own unique selectivity. The best selectivity obtained for acenaphthene and fluorene is methanol/water system for fluoranthene and pyrene is acetonitrile/water, and for benzo[g,h,i]perylene and dibenzo[a,h]anthracene is isopropanol/acetonitrile. So a three-stepwise gradient elution of multi-binary mobile phase can be chosen for separation of 16 PAHs.

Acenaphthenes↗

Incomplete degradation of polycyclic aromatic hydrocarbons in soil inoculated with wood-rotting fungi and their effect on the indigenous soil bacteria.

Soil artificially contaminated with fluorene, phenanthrene, pyrene, and benz[a]anthracene was inoculated with the wood-rotting fungi Plrurotus ostreatus and Antrodia vaillantii. During 12 weeks of incubation, polycyclic aromatic hydrocarbon (PAH) degradation and the formation of persistent degradation products were monitored by chemical analysis. In addition, the effect on the indigenous soil bacteria was studied by plate count techniques and by measuring the concentration of bacteria-specific phospholipid fatty acids (PLFAs). In both soils inoculated with fungi, the PAH degradation was enhanced compared to the control soil without fungi. The white-rot fungus P. ostreatus accelerated the degradation rate radically the first weeks, while the effect of the brown-rot fungus was more pronounced at later stages during the 12-week study. In a soil with no amendments, the final degradation result was similar to that in the soil with added fungi, although the degradation pattern for the individual PAHs was different. Furthermore, the degradation by P. ostreatus was accompanied by an accumulation of PAH metabolites, that is, 9-fluorenone, benz[a]anthracene-7,12-dione, and two compounds identified as 4-hydroxy-9-fluorenone and 4-oxapyrene-5-one, that was not seen in the other soils. The inoculation with the white-rot fungus also had a large negative effect on the indigenous soil bacteria. This could be an important drawback of using the white-rot fungus P. ostreatus in soil bioremediation since a sequential fungal-bacterial degradation probably is needed for a complete degradation of PAHs in soil. In the soil inoculated with A. vaillantii, on the other hand, no metabolites accumulated, and no negative effects were observed on the indigenous microorganisms.

Basidiomycota↗

Enhancement of polycyclic aromatic hydrocarbons removal during anaerobic treatment of urban sludge.

Anaerobically stabilized sewage sludge has potential to partially substitute synthetic fertilizers. The main risk with the recycling of urban sludge on agricultural soils is the accumulation of unwanted products, such as trace metals and organic micropollutants. In this context, the polycyclic aromatic hydrocarbons (PAHs) are particularly monitored because of their toxic properties at low concentrations and their high resistance to biological degradation. The aim of the present study was to optimize PAHs removal during anaerobic digestion of contaminated sewage sludge. Thirteen PAHs were monitored in laboratory-scale anaerobic bioreactors under mesophilic (35 degrees C) and thermophilic (55 degrees C) methanogenic conditions. Abiotic losses were statistically significant for the lightest PAHs, such as fluorene, phenanthrene and anthracene. It was shown that PAH removal was due to a specific biological activity. Biological PAHs removal was significantly enhanced by an increase of the temperature from 35 degrees C to 55 degrees C, especially for the heaviest PAHs. Bioaugmentation experiment was also performed by addition of a PAH-adapted bacterial consortium to a non-acclimated reactor. Significant enhancement of PAHs removal was observed. It was finally shown that PAH removal efficiencies and methanogenic performances were closely linked. The rate of biogas production may be used as an indicator of bacterial activity on PAH removal.

Bacteria, Anaerobic↗

[Characterization of polycyclic aromatic hydrocarbons dissolved in nonionic surfactants].

Using three typical nonionic surfactants (Tween80, Tween20 and Triton X-100), the solubilization of four kinds of polycyclic aromatic hydrocarbons (PAHs) e.g. naphthalene, phenanthrene, fluorene and pyrene, were characterized. It was found that not only nonionic surfactants could enhance the solubilization of PAHs greatly in the range of concentration above critical micellar concentration (CMC), but also the solubility had the linear relationship with the concentration of nonionic surfactants. The effect of solubilization enhancement at three surfactants was Triton X-100 > Tween80 > Tween20. In the three nonionic surfactants solution the micelle-aqueous phase partitioning coefficient (K(m)) had very good linear proportional to the octanol-water partitioning coefficient (Kow) for the four tested PAHs.

Octoxynol↗

[Changes in the activity of monoamine oxidase, adenylate cyclase and adenosine triphosphatase in liver cells during the process of hepatocarcinogenesis].

Activity of specific mitochondrial enzymes was studied in rat liver during 2-acetylamine fluorene or diethylnitrosamine-induced hepatocancerogenesis. The results of enzymatic activities studied correlated with morphological changes in cancerogenesis. Alterations in activity of monoamine oxidase, adenylate cyclase and adenosine triphosphatase depended on the step of cancerogenesis. Activity of adenylate cyclase in cell membranes decreased gradually during the impairment. Change in activity of the enzymes, observed at the step of enhanced liver cell proliferation, proceeded at further steps of cancerogenesis. The data obtained suggest that alterations in activity of mitochondrial enzymes are related to modified metabolism observed in the impaired cells.

2-Acetylaminofluorene↗

[Determination of soluble organic fraction in diesel exhaust particulates by gas chromatography/mass spectrometry].

The soluble organic fractions (SOF) in diesel exhaust particulates have been extracted with ultrasonic separator and analyzed by gas chromatography/mass spectrometry (GC/ MS). The GC/MS conditions were as follows: an HP SE-50 capillary column (30 m x 0.2 mm i. d. x 0.2 microm); temperature programming started at 100 degrees C, holding for 2.0 min, then increased to 160 degrees C at a rate of 4.0 degrees C /min, then to 250 degrees C at 8 degrees C/min, finally, kept at 250 degrees C for 31.75 min; boiling chamber temperature 260 degrees C; helium gas as carrier; chapiter pressure 45 kPa; sample size 1 microL; electron impact energy of mass spectrometer 70 eV; multiplier voltage 1 800 V; mass range 300 - 500 u. The results showed that under exhaust temperature, about 80% of SOF in particulates were normal or isomeric alkanes with carbon numbers from 9 to 28. The rest of the fractions of SOF were polycyclic aromatic hydrocarbons (homologs of indene, fluorene, phenanthrene, naphthalene etc.) and other organic substances. It is demonstrated that most of SOF were from unburned diesel and engine oils. The testing conclusion should be useful in designing and evaluating particulate filters.

Air Pollutants↗

[Nutritional treatment of hepatocellular carcinoma].

We investigated the relationship between the growth of HCC and nutrition, especially amino acids, and reconsidered the clinical application of amino acid imbalance. At first, rat chemical hepato-carcinogenesis was performed to investigate whether Aminoleban EN stimulates or restrains the occurrence of HCC. 2-Acetyl-amino-fluorene containing diet was administered intermittently according to Epstein's method. Rats were divided into two groups; group 1 was fed on Aminoleban EN containing diet and group 2 on a basal diet. There was no significant difference between the survival rate in the two groups. The average body weight of group 1 was significantly higher than that of group 2. The rats were sacrificed at the 25th week. All 11 rats of group 1 had no liver tumor, but 2 of 17 rats of group 2 had liver tumors, including a HCC and cholangiocellular carcinoma. The incidence of the liver tumor was significantly different between the two groups. Aminoleban EN could inhibit rat liver carcinogenesis, so it is considered to be a desirable nutritional product for LC patients from the stand point of cancer prevention. Secondly, the composition of amino acid was studied on HCC and surrounding tissue. There was no significant difference of Val, Leu, Leu, Phe, Tyr, Met and Fischer ratio between HCC and surrounding tissue.

Amino Acids↗

[Preparation and evaluation of monolithic silica columns for capillary electrochromatography].

A solution of methacryloxypropyltrimethoxysilane in the presence of an acid catalyst, water, toluene and azobisisobutyronitrile (AIBN) was initiated at 60 degrees C for 24 h in a 100 microm i.d. capillary to prepare a porous monolithic silica column by a one-step, in situ, process. Various parameters, such as the volume of applied voltage, buffer pH, acetonitrile concentration and column temperature, were varied to assess their influence on retention mechanism, electroosmotic flow (EOF) and column efficiencies. The heat initiated sol-gel capillary monolithic column showed reversed-phase behavior. Furthermore, the homogeneous reactor was obtained using surfactant (sodium dodecyl sulfate, SDS). The baseline separation of 9 neutral compounds (thiourea, benzene, toluene, ethyl benzene, n-propylbenzene, naphthalene, n-butylbenzene; fluorene and anthracene) and 7 acidic, basic and neutral compounds (thiourea, o-aminophenol, phenol, benzene, o-methylaniline, alpha-naphthylamine, 2,4-dichloroaniline) can be obtained under optimized capillary electrochromatographic conditions. Column efficiency of 110,000 plates/m was achieved for thiourea.

Alkanes↗

Enhancing the intrinsic bioremediation of PAH-contaminated anoxic estuarine sediments with biostimulating agents.

Estuarine sediments are frequently polluted with hydrocarbons from fuel spills and industrial wastes. Polycyclic aromatic hydrocarbons (PAHs) are components of these contaminants that tend to accumulate in the sediment due to their low aqueous solubility, low volatility, and high affinity for particulate matter. The toxic, recalcitrant, mutagenic, and carcinogenic nature of these compounds may require aggressive treatment to remediate polluted sites effectively. In petroleum-contaminated sediments near a petrochemical industry in Gwangyang Bay, Korea, in situ PAH concentrations ranged from 10 to 2,900 microg/kg dry sediment. To enhance the biodegradation rate of PAHs under anaerobic conditions, sediment samples were amended with biostimulating agents alone or in combination: nitrogen and phosphorus in the form of slow-release fertilizer (SRF), lactate, yeast extract (YE), and Tween 80. When added to the sediment individually, all tested agents enhanced the degradation of PAHs, including naphthalene, acenaphthene, anthracene, fluorene, phenanthrene, fluoranthene, pyrene, chrysene, and benzo[a]pyrene. Moreover, the combination of SRF, Tween 80, and lactate increased the PAH degradation rate 1.2-8.2 times above that of untreated sediment (0.01-10 microg PAH/kg dry sediment/day). Our results indicated that in situ contaminant PAHs in anoxic sediment, including high molecular weight PAHs, were degraded biologically and that the addition of stimulators increased the biodegradation potential of the intrinsic microbial populations. Our results will contribute to the development of new strategies for in situ treatment of PAH-contaminated anoxic sediments.

Anaerobiosis↗

Affinity alkylation of hamster hepatic arylamine N-acetyltransferases: isolation of a modified cysteine residue.

N-Acetyltransferases (NATs) play key roles in the detoxification and/or bioactivation of arylamines, arylhydroxylamines, arylhydroxamic acids, and hydrazines in mammalian tissues. In the present study, two hamster hepatic NATs (NAT I and NAT II) were separated, and each was purified greater than 2000-fold by sequential ammonium sulfate fractionation, DEAE anion exchange chromatography, Sephadex G-75 gel filtration chromatography, aminoazobenzene-coupled affinity chromatography, and DEAE anion exchange high performance liquid chromatography. Both NAT I and NAT II were purified to near-homogeneity. The molecular masses of NAT I and NAT II were estimated to be 30.5 kDa and 32.6 kDa, respectively. 2-(Bromoacetylamino)fluorene (Br-AAF) and bromoacetanilide were synthesized and evaluated as affinity labels for NAT I and NAT II. Whereas Br-AAF was a highly selective inactivator of NAT II, bromoacetanilide inactivated both NAT I and NAT II in a similar fashion. Inactivation of NAT II by both Br-AAF and bromoacetanilide, and inactivation of NAT I by bromoacetanilide, followed pseudo-first-order kinetics. Relative rate constants (k(obs)/[I]) for the two compounds indicate that Br-AAF is approximately 25 times more potent than bromoacetanilide as an inactivator of NAT II. Both acetylcoenzyme A (CoASAc) and 2-acetylaminofluorene protected NAT II from inactivation by Br-AAF, and CoASAc provided protection of both NAT I and NAT II activities from inactivation by bromoacetanilide, indicating that the inactivation by both bromoacetanilide and Br-AAF is active site directed. The irreversibility of the inactivation of NATs by Br-AAF and bromoacetanilide was demonstrated by the failure to recover transacetylase activities after gel filtration of enzyme preparations that had been preincubated with Br-AAF or bromoacetanilide. Preincubation of NAT II with CoASAc significantly reduced the incorporation of [14C]Br-AAF into the enzyme, providing further evidence that the labeling is active site directed. In addition, pretreatment of NAT II with N-ethylmaleimide completely prevented the labeling of NAT II with [14C]Br-AAF, which suggests that a cysteine thiol is the target nucleophile of Br-AAF. High performance liquid chromatography analysis of the hydrochloric acid hydrolysate of [14C]Br-AAF-labeled NAT II revealed that 70% of total radioactivity is associated with S-carboxymethyl-L-cysteine, indicating that Br-AAF reacts primarily with a cysteine residue at the active site. These studies provide direct evidence that hamster hepatic NAT II contains an essential cysteine residue at the active site, and they establish the potential utility of Br-AAF for determining amino acid sequences in the active site of hamster hepatic NAT II.

2-Acetylaminofluorene↗

Pegylated lysine based copolymeric dendritic micelles for solubilization and delivery of artemether.

PURPOSE: A newer polymeric amphiphilic micellar system was developed in the present study for solubilization and controlled delivery of an antimalarial drug, Artemether (ART). Methoxy polyethylene glycol (MPEG) 2000 and 5000 were used as hydrophilic terminal. METHODS: The hydrophobic di-Fluorene methoxycarbonyl-l-lysine (di-FMOC-L-lysine) was linked initially to the single reactive end of MPEG, and to the two amino groups of l-lysine by consecutive peptide linkages and deprotection upto 2.5 generations (G). Half-generations are diFMOC-lysine terminated systems and full-generations are deprotected l-lysine terminated systems. The half-generation (0.5 G, 1.5 G and 2.5 G) dendritic micelles of MPEG 2000 and 5000 were used to solubilize artemether. IR, NMR and Mass spectroscopy characterized the synthesis of these micellar systems. The CMC of the systems was determined. Then formulations made were characterized for solubility enhancement (i.e. drug loading) and drug-release profile. RESULTS: There is considerable solubility enhancement of artemether upto three to fifteen times depending on concentration, generation and type of dendritic micelles used. The size and shape were studied using transmission electron microscopy. The stability of the micellar formulation was also determined by storing the micelles at various temperatures for a definite period of time followed by its successive dilutions. The dendritic carriers were found to form stable micelles at 10-30 microg/ml (lower CMCs) depending on generation and type of MPEG used. The formulations increased the stability of the drug and also prolonged the release of artemether upto 1-2 days in vitro. CONCLUSION: From all the studies performed, it can be concluded that these micellar systems can be used for the safe and effective delivery of insoluble bioactive.

Artemether↗

[The specificity of the genotoxic action of carcinogenic aromatic compounds on Drosophila mus mutants].

Hypersensitivity to the toxic effect of benzo(a)pyrene (B(a)P) was determined in homozygous larvae of two D. melanogaster mus strains (mus 208B2 and mus210). The two others (mus205B1 and mus208B1) were found to be less sensitive and the parent strain was resistant. The lack of correlation between the sensitivity in larvae and the activity of aryl hydrocarbon hydroxylase in S15 fractions from adult flies whole body homogenates of the same strains was demonstrated. The hypertoxic effect of B(a)P and 2-acethylaminofluorene in strain mus210 seems to be rather specific because noncarcinogenic pyrene, benzo(e)pyrene and fluorene did not affect the survival of this most sensitive strain. Perspectives of the strain mus210 use for the environmental genotoxic pollutants screening were discussed.

Animals↗

[Studies of substances with antiviral activity. VI. Activity on Herpes simplex virus of bis-homoanalogs of nucleosides and of hydrazone derivatives of various aromatic substrates].

Derivatives of different chemical structures, namely hydrazones of aromatic compounds and bis-homoanalogues of pyrimidine and purine nucleosides, have been investigated for inhibiting activity on Herpes simplex virus infection of human HEp-2 cell cultures. Some thiosemicarbazones, nucleoside analogues and guanylhydrazones proved active [compounds (I), (II b), (II c), (III), (IV a), (IV b), (V a), (V b); Fig. 1]. An increase in the number of guanylhydrazone chains linked to a fluorene structure [from 1 to 3: compounds (II a), (II b) and (II c)] increased the "activity index" (i.e., toxic versus active concentrations: Table II). Further in vitro investigations have been carried out on bis-guanylhydrazone of 1-phenyl-2-chloro-3,7-diformylindole (I) and it was found that its activity is of the order of 1 microgram per ml (Fig. 3). The compound completely blocks low multiplicity infections while it only blocks cytopathogenicity, not viral replication, in high multiplicity infections.

Antiviral Agents↗

Mucopolysaccharidosis (MPS) in ocular tissues as induced by amphiphilic di-cationic drugs.

The immunostimulatory drug tilorone (2,7-bis(2- (diethylamino)ethoxy)-9H-fluorene-9-one) has previously been described to induce keratopathy in patients and in rats; in the latter, lysosomal storage of sulfated glycosaminoglycans (mucopolysaccharidosis, MPS) was found to be the reason for corneal clouding. In the present histochemical and ultrastructural study, several ocular tissues of rats were examined after chronic treatment with tilorone and two other immunostimulatory agents (3,6-bis(2-(dipiperidyl)ethoxy)-acridine and the diethylamino analogue). The acridine derivatives hardly affected the cornea and sclera. Tilorone as well as the acridine derivatives induced significant MPS in ciliary body, iris, and choroid. While the functional consequences of drug-induced MPS in ocular tissues are not known yet, except for the cornea, this adverse drug action should be taken into account when new compounds are designed that share certain physicochemical features with tilorone. One molecular feature essential for the MPS-inducing potency of a drug appears to be the dicationic amphiphilic character.

Acridines↗

Inactivation of 1,3-, 1,6-, and 1,8-dinitropyrene by cytochrome P-450 enzymes in human and rat liver microsomes.

NADPH-fortified human liver microsomes were examined with regard to ability to detoxicate several chemicals that do not require enzymatic oxidation to elicit a genotoxic response in a Salmonella typhimurium TA1535/pSK1002 system where umu response is used as an indicator of DNA damage. Microsomes did not affect the response seen with daunomycin, mitomycin C, 2,4,7-trinitro-9-fluorene, 1-nitropyrene, doxorubicin, 1-methyl-3-nitro-1-nitrosoguanidine, 2-nitrofluorene, or 1-ethyl-3-nitro-1-nitrosoguanidine (cited in order of decreasing umu response per mol). Human and rat liver microsomes did inactivate 1,3-, 1,6-, and 1,8-dinitropyrene; with human liver microsomes the activity of 1,3-dinitropyrene was most strongly inhibited, while with rat liver microsomes the genotoxicities of all three dinitropyrenes were inhibited to a similar extent. NADPH-cytochrome P-450 reductase was demonstrated to inactivate 1,6- and 1,8-dinitropyrene but not 1,3-dinitropyrene. Both rat cytochrome P-450 beta NF-B (P-450 IA1) and P-450ISF-G (P-450 IA2) inactivated 1,3-dinitropyrene, with the former being more effective. Correlation studies done with liver microsomes prepared from variously treated rats and immunoinhibition studies suggest that cytochrome P-450 beta NF-B and P-450ISF-G are both involved in the detoxication of all three of the dinitropyrenes in rat liver microsomes. In a series of assays done with various human liver microsomal preparations, the inactivation of the three dinitropyrenes was not correlated to each other at all. Correlation analysis and inhibition studies with 7,8-benzoflavone and antibodies indicate that human cytochrome P-450 enzymes in the IA family are most effective in detoxicating this compound; the contribution of cytochrome P-450PA (P-450 IA2, the phenacetin O-deethylase) is deemed more important, but a role for the small amount of cytochrome P1-450 (P-450 IA1) in the liver cannot be ruled out. In contrast to the case of 1,3-dinitropyrene, the inactivation of 1,6-dinitropyrene is well correlated with levels of cytochrome P-450NF (P-450 IIIA4, nifedipine oxidase) and its catalytic activities. The inactivation of 1,8-dinitropyrene was not correlated with any of the above parameters and only correlated with the conversion of benzo(a)pyrene to its 3-hydroxy and 4,5-dihydrodiol products, for which the principal enzymes involved in human liver are unknown. Thus, distinct human cytochrome P-450 enzymes are involved in the detoxication of different dinitropyrene congeners, and the situation appears to contrast with that in rat liver.

Animals↗

[Polycyclic aromatic hydrocarbons in the atmosphere in the town of Zenica].

The content of some polycyclic aromatic hydrocarbons in extracts of particulate matter collected in the city of Zenica in December 1987 was analysed. In addition to the presence of proven carcinogens like benzo(a)pyrene, benzo(a)anthracene, chryzene and dibenzo(a,h)anthracene, the contents of naphthalene, fluorene, fenanthrene, anthracene, fluoranthene and pyrene were also determined. Those substances were rightly assumed to be precursors of genotoxic products in reactions with atmospheric nitrogen oxides. The determined average concentration of benzo(a)pyrene was higher than those found in other places in Yugoslavia where similar studies were conducted. At the same time, the measured benzo(a)pyrene concentration exceeded the guidelines for inhabited places according to the standards of the Federal Republic Germany and the Netherlands. The observed high variations in naphthalene concentration of as much as two orders of magnitude in two days were likely due to unsolved technological problems.

Air Pollutants↗

Influence of cell proliferation on initiating activity of pure polychlorinated biphenyls and complex mixtures in resistant hepatocyte in vivo assays for carcinogenicity.

The abilities of various pure polychlorinated biphenyls (PCB) and complex mixtures to generate resistant gamma-glutamyltransferase (GGT)-positive hepatocellular nodules was evaluated in F344 rats in which hepatocytes were proliferating. The PCB examined were 2,2',4,4',5,5'-hexachlorobiphenyl (CAS: 35065-27-1), 2,2',4,4'-tetrachlorobiphenyl, 2,2',5,5'-tetrachlorobiphenyl, Aroclor 1254 (CAS: 11097-69-1), and a prepared mixture of pure PCB isomers and congeners similar to those found in human breast milk. The PCB were administered either to male and female suckling rats (weekly for 3 wk) during liver growth or to adult male rats (150-160 g body wt) previously subjected to two-thirds partial hepatectomy (PH). Rats were subsequently given a selection regimen consisting of 3 daily doses (20 mg/kg) of 2-acetylamino-fluorene (2-FAA; CAS: 53-96-3) followed by either PH or necrotizing carbon tetrachloride (CAS: 56-23-5) in adult rats that previously underwent PH. None of the PCB exposures generated GGT-positive nodules after selection, whereas known initiators such as diethylnitrosamine (CAS: 55-18-5), 3-methylcholanthrene (CAS: 56-49-5), benzo[a]pyrene (CAS: 50-32-8), and 2-FAA were active initiators of nodules in suckling or hepatectomized rats. These findings indicate that short-term exposures to these PCB during liver cell proliferation do not show initiating action in an in vivo assay that detects both hepatic and nonhepatic initiating carcinogens.

Animals↗