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PubMed1990

Tissue-specific expression of murine keratin K13 in internal stratified squamous epithelia and its aberrant expression during two-stage mouse skin carcinogenesis is associated with the methylation state of a distinct CpG site in the remote 5'-flanking region of the gene.

Under normal conditions, the expression of the murine type-I keratin K13 is restricted to the suprabasal, differentiating cell layers of internal stratified squamous epithelia that line the oral cavity and the upper digestive tract. It is, however, also expressed aberrantly but constitutively in only the differentiating parts of 7,12-dimethylbenz[alpha]anthracene/12.0-tetradecanoyl-phorbol-13-acetate (DMBA/TPA) induced malignant epidermal tumors of the back skin of mice, whereas its likewise suprabasal expression in papillomas is highly variable [27]. In an approach to unravel regulatory DNA sequence elements involved in the tissue-specific and aberrant K13 expression, the 5'-flanking region of the gene was analyzed with regard to potential methylation sites and DNase hypersensitive regions. We report on the identification of a CpG dinucleotide (designated M1; located about 2.3 kb upstream of the transcriptional start site), whose methylation state correlates with the differential gene activity in various epithelia and tumors. We show that in K13-nonexpressing integumental epidermis the M1 site is methylated in both suprabasal and basal cells. In contrast, internal stratified squamous epithelia (i.e. tongue, esophagus, forestomach) exhibit an unmethylated M1 site not only in their suprabasal. K13-expressing cells, but also in basal cells--in which, however, the keratin is not yet synthesized. The identical situation is encountered in DMBA TPA-induced moderately differentiating epidermal squamous cell carcinomas with compartmentalized K13 expression. In papillomas we observed a striking correlation between the extent of both suprabasally expressed K13 protein and demonstrable DNA copies carrying an unmethylated M1 site. Moreover we found that the sequence region around the M1 site was DNAseI hypersensitive in K13-expressing malignant tumors, but DNaseI insensitive in K13-nonexpressing epithelia and cells. DNAseI hypersensitivity in K13-expressing tissues was, however, independent of an active transcription of the gene in differentiating cells or transcriptional inertia in basal cells. These results strongly suggest that the sequence element around the demethylated M1 site is involved in a multi-level control mechanism mediating the selective expression of the K13 gene in internal squamous epithelia and in DMBA/TPA-induced epidermal tumors.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1998

Assessment of whole body L-leucine oxidation by noninvasive L-[1-13C]leucine breath tests: a reappraisal in patients with maple syrup urine disease, obligate heterozygotes, and healthy subjects.

Suitability of a recently proposed noninvasive L-[13C]leucine breath test for assessment of whole body leucine oxidation in maple syrup urine disease (MSUD) was examined. Oral L-[1-13C]leucine loads (38 micromol/kg body weight) were performed in overnight fasted MSUD patients (n = 6, classical form), obligate heterozygote parents (n = 6), and control subjects (n = 10). Three-hour 13CO2 exhalation kinetics were evaluated using curve fitting procedures. Venous blood was obtained in most cases and analyzed for 13C-labeled plasma metabolites. In control subjects, maximal 13CO2 exhalation was reached at tmax = 55 +/- 18 min. Cumulative 13CO2 output at 3 h amounted to 4.7 +/- 0.7 micromol x (kg body weight)(-1). Estimated total 3CO2 exhalation was 7.2 +/- 1.4 micromol x (kg body weight)(-1) (19.0 +/- 3.6% of the dose). Half of this amount was expired at t1/2 = 130 +/- 18 min. The data show a considerable degree of intersubject variability. Intraindividual variability was comparable, however, when checked in two volunteers. In obligate heterozygotes, 13CO2 kinetics were similar to controls (tmax = 35 +/- 8 min, t1/2 = 95 +/- 16 min). Total 13CO2 output [5.7 +/- 1.4 micromol x (kg body weight)(-1)] tended to be in the lower control range. None of the MSUD patients under study exhibited a significant increase in 13CO2 output after load. Maximal increase of label in plasma 4-methyl-2-oxopentanoate, the physiologic precursor of 13CO2, was 16.1 +/- 3.5 MPE in control subjects. In MSUD, label dilution was increased and correlated with the patients' leucine/4-methyl-2-oxopentanoate plasma levels. Considering the generally high variability of 13CO2 output and the unstable substrate pools in MSUD, we discuss the limitations of whole body leucine oxidation measurements by noninvasive approaches.

Adolescent↗

PubMed1992

Protective effect of the NMDA antagonist MK-801 on photochemically induced spinal lesions in the rat.

Photochemically induced ischemic lesions in the rat spinal cord were studied using neurological tests and morphological evaluation in order to investigate ischemia-mediated pathophysiological mechanisms in traumatic spinal cord injury. One week after ischemic lesioning, animals were severely impaired with 85% decrease of performance in neurological tests. During the next 2 weeks considerable recovery occurred. Pretreatment with the noncompetitive N-methyl-D-aspartate antagonist MK-801 at a dose of 0.5-1.0 mg/kg significantly improved the recovery of function after spinal ischemia while lower doses exerted no protection. Morphologically, no dose-response effect on the extent of tissue necrosis was found, but a significant difference between groups with severe neurological deficit versus mildly affected groups was observed. Immunohistochemical staining for glial fibrillary acidic protein in the area close to the lesion revealed extensive gliosis, while neurofilament immunohistochemistry showed an irregular pattern of fiber loss with large variability between animals. The degree of gliosis or loss of neurofilament immunoreactivity in nonnecrotic tissue was not affected by MK-801. These results suggest that excessive stimulation of N-methyl-D-aspartate receptors participates in the development of spinal cord ischemia and possibly also participates after traumatic spinal cord injury.

Animals↗

PubMed2004

The distribution and inventory of total and methyl mercury in Kuwait Bay.

Sediment (surface and core) sampling was conducted during the period from August 96-December 98 from intertidal and offshore areas in Kuwait Bay. The highest (and most variable) concentrations of total mercury (T-Hg; 36500+/-34930 ng g(-1)) are encountered around the previous industrial outfall where sediments are disturbed by shipping activities. The concentrations of T-Hg are lower in the Shuwaikh Port area (650+/-210 ng g(-1)) and continue to decrease towards the northern coastline of Kuwait Bay (average concentrations in the wider Bay region are 50+/-30 ng g(-1)). These values are still above background concentrations of 15-20 ng g(-1). Calculation of the total inventory of mercury in all the surface sediments of the studied area indicates that approximately 22.5 ton is present which is similar to the estimated industrial discharges of approximately 20 ton suggesting that the contamination is largely confined to the Bay and that releases to the wider Gulf region are small. The distributions of MeHg are similar to those of T-Hg and represent ranges between 0.23% and 0.5% of the T-Hg indicating that surface sediments within Kuwait Bay contain approximately 80 kg of this chemical.

Environmental Monitoring↗

PubMed1998

Structural analysis of the phase-variable lipooligosaccharide from Haemophilus somnus strain 738.

The structure of the phase variable lipooligosaccharide (LOS) from Haemophilus somnus strain 738 was elucidated. The LOS was subjected to a variety of degradative procedures. The structures of the purified products were established by monosaccharide and methylation analyses, NMR spectroscopy and mass spectrometry. The following structures for the two major components were determined on the basis of the combined data from these experiments. [structure in text]. In the structures Kdo is 3-deoxy-D-manno-octulosonic acid, PEtn is phosphoethanolamine, PCho is phosphocholine, Hep is L-glycero-D-manno-heptose, and the remaining glucose units have the D configuration. The elucidation of these structures has increased our understanding of the relationship between the phase-variable LOS and the pathogenic potential of this organism.

Haemophilus↗

PubMed2001

The potential for toxic effects of chronic, low-dose exposure to organophosphates.

Organophosphorus esters have the potential to produce several forms of toxicity. Most produce acute intoxication as a result of inhibition of acetylcholinesterase and, if severe, this can have longer lasting secondary consequences such as intermediate syndrome, or even permanent disability. Some esters produce a very specific syndrome of delayed peripheral neuropathy. This neuropathy is always preceded by severe acute intoxication, except in the case of a few specific agents such as tri-o-cresyl phosphate. All of these effects are reasonably well understood and show a dose threshold. Chronic low level exposure in non-poisoned subjects has been associated with impaired neurobehavioral performance in some, but not all, epidemiological studies. The mechanisms involved are not well understood, but if organophosphates do play a causal role, this will not necessarily be via acetylcholinesterase inhibition. Doses too low to produce cholinergic signs have been shown to produce a variety of effects in experimental animals ranging from enhanced maze learning to slowed nerve conduction. It is likely that other, more sensitive, brain proteins are the targets for such actions. Effects mediated via such target proteins would be expected to show very different structure-activity relationships to acute toxicity mediated by acetylcholinesterase. Hence epidemiological studies expecting similar (class) effects from low-dose exposure to different organophosphorus esters may produce variable results or false negatives.

Animals↗

PubMed2002

Variability analyses suggest that supraspino-spinal interactions provide dynamic stability in motor control.

Effects of supraspino-spinal feedforward-feedback (FF-FB) interactions on variability in locomotor rhythm and coordination were examined in in vitro brain-spinal cord lamprey preparations. Spinal locomotor networks were activated by applying 0.2 mM N-methyl-DL-aspartate (NMA) to three spinal pools: gill, rostral and caudal. Bathing the brain with zero Ca(2+) saline altered supraspinal-spinal drive and FF-FB interaction while spino-supraspinal feedback was changed by applying NMA to the caudal pool only. Wavelet analyses indicated a non-uniform energy distribution in ventral root (VR) activity that shifted between frequency bands on FF-FB interruption. Wavelet analysis was used to extract 300-s long epochs of low frequency burst rhythm. These were analyzed using a sliding-window time-varying covariance method. From the autocovariance in each window, the cycle period and height of the first side lobe peak were determined. Rostral VR variability (determined from standard deviation and coefficient of variation of all cycle periods and the mean peak height) was significantly higher than caudal VR variability. FF-FB interruption significantly decreased the rostral VR cycle period and variability but the rostro-caudal gradient remained. The intersegmental delay was also affected. The caudal VR rhythm with NMA in the caudal pool only was slower but more variable than with NMA over the entire cord. These results indicate that the locomotor rhythm in the presence of supraspino-spinal interactions is slower but has a higher variability. The higher variability may reflect a dynamic stability of the system. Additionally, differences in local neural organization likely contribute to rostro-caudal differences in variability of the motor output.

Algorithms↗

PubMed1993

Mitochondrial 2-methylacetoacetyl-CoA thiolase deficiency: an inborn error of isoleucine and ketone body metabolism.

A review is presented of 22 published cases of verified or probable mitochondrial 2-methylacetoacetyl-CoA thiolase deficiency, a disorder of isoleucine and ketone body metabolism. The clinical expression, characterized by ketoacidosis, vomiting and lethargy, is highly variable. Typical age of onset is between 6 and 24 months. The disorder, which has been observed in several ethnic groups, is apparently inherited as an autosomal, recessive trait. The prognosis is relatively good if acute episodes of ketoacidosis and dehydration are adequately treated. There is abnormal urinary excretion of 2-methyl-3-hydroxybutyric acid, tiglylglycine, and in some instances also 2-methyl-acetoacetic acid. However, such a pattern of organic aciduria has also been found in cases with normal thiolase activity. Genetic complementation analyses have demonstrated considerable heterogeneity. The cDNA for human methyl-acetoacetyl-CoA thiolase has been cloned and sequenced. Studies in one patient showed a G-to-A substitution at position 1138 of the mRNA, causing 347Ala to Thr change in the mature enzyme. Studies in other patients have shown variable enzyme amount and/or stability.

Acetyl-CoA C-Acyltransferase↗

PubMed1977

Reversal by vitamin A analogues (retinoids) of hyperplasia induced by N-methyl-N'-nitro-N-nitrosoguanidine in mouse prostate organ cultures.

The antihyperplastic activity of beta-retinoic acid (RA) and nine synthetic analogues (retinoids) was examined in organ cultures of mouse prostate made hyperplastic by treatment with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). After 8 or 10 days, when most explants developed hyperplasia, the carcinogen was withdrawn and explants were incubated in control medium and medium containing different concentrations of a retinoid. The antimitotic activity of retinoids was compared with that of RA. Different retinoids produced variable degrees of mitotic inhibition in the hyperplastic prostate epithelium. The methylketo cyclopentenyl and 1-methoxyethyl cyclopentenyl analogues of RA were at least 50-fold more active than RA in reversing MNNG-induced hyperplasia. The trimethylmethoxyphenyl analogue of RA and retinyl methyl ether were significantly more active than RA. Three analogues, N-acetyiretinylamine, retinal acetyl hydrazone, and retinal oxime, were as active as RA. The chlorotrimethylphenyl analogue showed less activity than RA, and alpha-retinyl acetate was completely devoid of mitotic inhibitory activity.

Cell Division↗

PubMed1992

Structural variability in the glucuronoxylomannan of Cryptococcus neoformans serotype A isolates determined by 13C NMR spectroscopy.

Cryptococcus neoformans, the etiologic agent of cryptococcal meningoencephalitis, produces glucuronoxylomannan (GXM) as the major capsule component. Purified GXMs obtained from eight serotype A isolates of C. neoformans were treated by ultrasonic irradiation and then O-deacetylated prior to their comprehensive chemical analysis by GLC, GLC-MS, and 13C NMR spectroscopy. The average xylose: mannose: glucuronic acid molar ratio of the eight isolates is 1.96 +/- 0.25: 3.00: 0.58 +/- 0.10. Methylation analyses and 13C NMR spectroscopy show a general structure for GXM that is comprised of a linear (1----3)-alpha-D-mannopyranan substituted with beta-D-GlcpA and with beta-D-Xylp at O-2. Variable quantities of unsubstituted (1----3)-alpha-D-Manp were observed between the eight isolates studied. In several isolates some of the (1----3)-alpha-D-Manp residues are disubstituted with beta-D-GlcpA at O-2 and with beta-D-Xylp at O-4; this type of substitution was not previously thought to occur in serotype A isolates. Heterogeneity, between isolates, in the disposition of the substituents along the mannopyranan backbone was revealed by 13C NMR spectroscopy. The eight isolates, and three isolates previously studied, were each assigned to one of four distinct groups based on the 13C NMR chemical shifts of the anomeric carbons. Six of the eleven isolates gave identical spectra (Group I). The six major anomeric resonances from Group I were assigned to specific glycosidic linkages present in GXM. The remaining five isolates gave more complex spectra that are indicative of additional linkages and comprise the remaining three groups. Three of these five isolates contain substantial amounts of linkages previously thought to be distinctive of serotypes B and C, i.e., Manp residues that are 4-O-glycosylated with beta-D-Xylp. Methylation analyses only predicted an average repeating unit, whereas 13C NMR spectroscopy demonstrated that GXM from each isolate may be categorized into four groups by the occurrence of distinct sequences of carbohydrate residues.

Carbohydrate Sequence↗

PubMed2003

Incremented alkyl derivatives enhance collision induced glycosidic bond cleavage in mass spectrometry of disaccharides.

Electrospray ionization and collision induced dissociation on a triple quadrupole mass spectrometer were used to determine the effect of spatial crowding of incremented alkyl groups of two anomeric pairs of peralkylated (methyl to pentyl) disaccharides (maltose/cellobiose and isomaltose/gentiobiose). Protonated molecules were generated which underwent extensive fragmentation under low energy conditions. For both the 1 --> 4 and 1 --> 6 alpha and beta isomers, at comparable collision energies the methyl derivative exhibited the least fragmentation followed by ethyl, propyl, butyl, and pentyl. Collision energy is converted to rotational-vibrational modes in competition with bond cleavage, as represented by the slope of product/parent ion (D/P) ratio versus offset energy. Variable rotational freedom at the glycosidic linkage with incremented alkyl groups is hypothesized to be responsible for this effect. Discrimination of anomeric configuration was also assessed for these stereoiosmeric disaccharides. A systematic study showed that an increasing discrimination was attained for the 1 --> 4 isomeric pair as the size of the derivative increased from methyl to pentyl. No anomeric discrimination was attained for the 1 --> 6 isomeric pair. Parent and product ion scans confirmed the consistency of fragmentation pathways among derivatives. Chem-X and MM3 molecular modeling programs were used to obtain minimum energy structures and freedom of motion volumes for the permethylated disaccharides. The modeling results correlated with the fragmentation ratios obtained in the mass spectrometer giving strong indication that the collision induced spectra are dependent on the freedom of rotational motion around the glycosidic bond.

Algorithms↗

PubMed1999

Voltage-dependent properties of dendrites that eliminate location-dependent variability of synaptic input.

We examined the hypothesis that voltage-dependent properties of dendrites allow for the accurate transfer of synaptic information to the soma independent of synapse location. This hypothesis is motivated by experimental evidence that dendrites contain a complex array of voltage-gated channels. How these channels affect synaptic integration is unknown. One hypothesized role for dendritic voltage-gated channels is to counteract passive cable properties, rendering all synapses electrotonically equidistant from the soma. With dendrites modeled as passive cables, the effect a synapse exerts at the soma depends on dendritic location (referred to as location-dependent variability of the synaptic input). In this theoretical study we used a simplified three-compartment model of a neuron to determine the dendritic voltage-dependent properties required for accurate transfer of synaptic information to the soma independent of synapse location. A dendrite that eliminates location-dependent variability requires three components: 1) a steady-state, voltage-dependent inward current that together with the passive leak current provides a net outward current and a zero slope conductance at depolarized potentials, 2) a fast, transient, inward current that compensates for dendritic membrane capacitance, and 3) both alpha amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid- and N-methyl-D-aspartate-like synaptic conductances that together permit synapses to behave as ideal current sources. These components are consistent with the known properties of dendrites. In addition, these results indicate that a dendrite designed to eliminate location-dependent variability also actively back-propagates somatic action potentials.

Action Potentials↗

PubMed1982

[Pathogenesis of hyperlipidemia and fatty liver of rabbits induced by methyl iodide. Increased synthesis and secretion of triglyceride in the liver].

Male Japanese white rabbits were injected subcutaneously with methyl iodide (57 mg/kg body weight/day) on two successive days and their lipid metabolism was investigated 48 hr after the last injection. The plasma triglyceride levels increased from the preinjection average of 56.1 mg/dl to 246.0 mg/dl on an average, the individual values being greatly variable. Analysis of lipoprotein profile of plasma showed a significant increase of very low density lipoproteins (VLDL). Lipolytic activities in postheparin plasma did not change. However, rates of triglyceride secretion into plasma, measured by Triton WR 1339 injection method, were significantly higher in the animals treated with methyl iodide than in the controls. Histological investigation of the liver showed diffuse fat deposits in the hepatocytes without any destructive and inflammatory changes. The results indicate that hyperlipidemia and fatty liver of rabbits induced by methyl iodide is related to the elevation of triglyceride synthesis and its secretion in the liver.

Animals↗

PubMed2001

Role of kainate receptor activation and desensitization on the [Ca(2+)](i) changes in cultured rat hippocampal neurons.

We investigated the role of kainate (KA) receptor activation and desensitization in inducing the increase in the intracellular free Ca(2+) concentration ([Ca(2+)](i)) in individual cultured rat hippocampal neurons. The rat hippocampal neurons in the cultures were shown to express kainate receptor subunits, KA2 and GluR6/7, either by immunocytochemistry or by immunoblot analysis. The effect of LY303070, an alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA) receptor antagonist, on the alterations in the [Ca(2+)](i) caused by kainate showed cell-to-cell variability. The [Ca(2+)](i) increase caused by kainate was mostly mediated by the activation of AMPA receptors because LY303070 inhibited the response to kainate in a high percentage of neurons. The response to kainate was potentiated by concanavalin A (Con A), which inhibits kainate receptor desensitization, in 82.1% of the neurons, and this potentiation was not reversed by LY303070 in about 38% of the neurons. Also, upon stimulation of the cells with 4-methylglutamate (MGA), a selective kainate receptor agonist, in the presence of Con A, it was possible to observe [Ca(2+)](i) changes induced by kainate receptor activation, because LY303070 did not inhibit the response in all neurons analyzed. In toxicity studies, cultured rat hippocampal neurons were exposed to the drugs for 30 min, and the cell viability was evaluated at 24 hr using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The selective activation of kainate receptors with MGA, in the presence of Con A, induced a toxic effect, which was not prevented by LY303070, revealing a contribution of a small subpopulation of neurons expressing kainate receptors that independently mediate cytotoxicity. Taken together, these results indicate that cultured hippocampal neurons express not only AMPA receptors, but also kainate receptors, which can modulate the [Ca(2+)](i) and toxicity.

Animals↗

PubMed1993

Identification of P450 enzymes involved in metabolism of verapamil in humans.

The calcium channel blocker verapamil[2,8-bis-(3,4-dimethoxyphenyl)-6-methyl-2-isopropyl-6- azaoctanitrile] is widely used in the treatment of hypertension, angina pectoris and cardiac arrhythmias. The drug undergoes extensive and variable hepatic metabolism in man with the major metabolic steps comprising formation of D-617 [2-(3,4-dimethoxyphenyl)-5-methylamino-2-isopropylvaleronitrile] and norverapamil [2,8-bis-(3,4-dimethoxyphenyl)-2-isopropyl-6-azaoctanitrile]. The enzymes involved in metabolism of verapamil have not been characterized so far. Identification of these enzymes would enable estimation of both interindividual variability in verapamil metabolism introduced by the respective pathway and potential for metabolic interactions. We therefore characterized the enzymes involved in formation of D-617 and norverapamil. The maximum rate of formation of D-617 and norverapamil was determined in the microsomal fraction of 21 human livers which had been previously characterized for the individual expression of various P450 enzymes (CYP1A2, CYP2C, CYP2D6, CYP2E1 and CYP3A3/4) by means of Western blotting. Specific antibodies directed against CYP3A were used to inhibit formation of D-617 and norverapamil. Finally, formation of both metabolites was investigated in microsomes obtained from yeast cells which were genetically engineered for stable expression of human P450. Formation of D-617 was correlated with the expression of CYP3A (r = 0.85; P < 0.001) and CYP1A2 (r = 0.57; P < 0.01) in the microsomal fraction of 21 human livers after incubation with racemic verapamil.(ABSTRACT TRUNCATED AT 250 WORDS)

Biotransformation↗

PubMed1987

Kinetics of hexobarbital and dipyrone in critical care patients receiving high-dose pentobarbital.

The effect of pentobarbital treatment in a mean dose of 30 mg/kg/day on the clearance of hexobarbital (Evipan) and dipyrone (Novalgin) has been evaluated in critical care patients receiving a large number of drugs as comedication. Eleven patients treated with pentobarbital showed a hexobarbital half-life of 2.79 h and a total plasma clearance of 9.80 ml X min-1 X kg-1 as compared to 10 patients without pentobarbital administration in whom there was a significantly longer half life (6.92 h) and lower clearance (2.97 ml X min-1 X kg-1). The kinetics of hexobarbital were correlated with the urinary excretion of D-glucaric acid, a non-invasive parameter of drug metabolising activity. In 10 patients on pentobarbital, the total plasma clearance of N-4-methyl-aminoantipyrine, the active form of dipyrone, did not differ from that in 8 patients not receiving pentobarbital. As drug kinetics show great variability in these patients, it is difficult to discriminate enzyme induction from other mechanisms, for example competitive inhibition or changes in volume of distribution. In the presence of pentobarbital, however, induction of drug metabolising enzymes should be considered as a possible reason for the higher clearance of hexobarbital.

Adult↗

PubMed1992

Nitric oxide synthase inhibitors cause sustained, but reversible, hypertension and hindquarters vasoconstriction in Brattleboro rats.

Homozygous male Brattleboro rats were given a solution of NG-monomethyl-L-arginine (L-NMMA; 1 mg ml-1) to drink for a period of 7 days. There was a persistent elevation of mean arterial blood pressure, accompanied by a significant hindquarters vasoconstriction. Within 9 h of withdrawal of L-NMMA all variables were not different from pre-L-NMMA values. Brattleboro rats (n = 3) which had been drinking NG-nitro-L-arginine methyl ester (L-NAME) solution (0.05 mg ml-1) for 5-6 months showed an increased blood pressure which reversed to normal within 48 h after withdrawing the L-NAME. Thus, inhibition of nitric oxide synthesis leads to long-lasting, but reversible, hypertension.

Amino Acid Oxidoreductases↗

PubMed1985

Predictive correlations for the toxicity of alkyl- and halogen- substituted phenols.

The structure-activity relationships between toxicity (log BR), monitored as cell population growth, and the log 1-octanol/water partition coefficient (log Kow) for a series of 20 alkyl- and halogen-substituted phenols have been examined. The equation log BR = 0.9455 log Kow -1.9190 has been found to be an excellent linear model for these compounds. It explains 93.8% of the variability in toxicity. Subdivision of the tested derivatives based on substituent field electronic effects reveals that those with electron-releasing effects, e.g. methyl or ethyl groups, are slightly less toxic than those with electron-withdrawing effects, e.g. halogen groups.

Electrons↗