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Biomedical subjects

J R Olson

Publications and source records attributed to J R Olson.

At least 37 records · Page 2Linked to original sources
PubMed1989

Species differences in estrogen receptors and in the response to 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure.

The acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exhibits marked interspecies variability, with the guinea-pig, rat and hamster representing the species most sensitive, intermediate and most resistant to acute toxicity. Prepubertal guinea-pigs, rats and hamsters were treated with a single intraperitoneal injection of TCDD in olive oil at doses of 4, 50 and 1500 micrograms/kg, respectively. These exposures were chosen to produce acute toxicity and all 3 species exhibited a decrease in the rate of body weight gain during the 7 days following TCDD exposure when compared with control (olive oil-treated) animals. On the 7th day after exposure, the density and affinity of 17 beta-estradiol receptors were determined in the uterus and liver of TCDD-treated and control animals. The treatment with TCDD did not alter the affinity of the receptors in these 3 species. The density of hepatic 17 beta-estradiol receptors was decreased 65% in the guinea pig and 92% in the rat following exposure to TCDD. In contrast, TCDD-treated hamsters exhibited no change in the density of hepatic 17 beta-estradiol receptors. The uterine 17 beta-estradiol receptors were increased in density by TCDD treatment in the hamster and in the rat when expressed per mg protein. Uterine wet weights in the guinea-pig and rat were also significantly decreased by TCDD treatment but were not changed in the hamster. When the Bmax for uterine 17 beta-estradiol receptors was expressed as pmol/g tissue wet weight. TCDD exposure was found to produce an 11% decrease in density in the rat, while producing a 44% increase in the hamster. In control animals, the density of uterine 17 beta-estradiol receptors correlated inversely with the lethal dose of TCDD in these 3 species (i.e., the guinea-pig has the lowest LD50 and highest density of uterine 17 beta-estradiol receptors). The different responses to TCDD in the 3 species suggest that the changes in 17 beta-estradiol receptors may be related to species-specific toxic responses associated with TCDD exposure.

Animals↗
PubMed1989

Comparison of three methods of estimating energy expenditure: caltrac, heart rate, and video analysis.

This study examined the accuracy of a new device (Caltrac) in estimating energy expenditure via acceleration measurements. Energy expenditure of 20 high school students during basketball class activity (average length = 37 min) was estimated using the Caltrac, heart rate recording, and video analysis. Heart rate recording and video analysis estimates of energy expenditure were determined from heart rate, caloric expenditure curves, and an activity rating scale, respectively. The following estimates of caloric expenditure (M +/- SD) were found: heart rate recording = 196 +/- 73 greater than Caltrac = 163 +/- 49 greater than film analysis = 123 +/- 30 kcal (p less than .05). Laboratory simulations of the basketball activity revealed that the Caltrac energy expenditure was not significantly different from the actual energy expenditure (p greater than .05). The heart rate recording and video analysis estimates of energy expenditure were significantly (p less than .05) higher and lower, respectively, than the actual energy expenditure. The Caltrac is a lightweight, low-cost device that provides a relatively accurate estimate of energy expenditure in free-ranging activities, such as basketball.

Adolescent↗
PubMed1989

Project IDEA: International Deaf Education Association.

This paper addresses some of the difficulties of educating the deaf in third world countries. Project IDEA (International Deaf Education Association) is an exemplary program started by the Peace Corps in Bohol, Philippines. The author made an on-sight visit to this project in 1986. Additionally, two Montana State University students completed internships there in early 1988 and their detailed accounts help form the basis for this descriptive report on the newly formed Bohol deaf community and their special educational/vocational program.

Adolescent↗
PubMed1989

Cell specific enzyme markers as indicators of neurotoxicity: effects of acute exposure to methylmercury.

In order to assess the sensitivity of several cell specific enzyme markers (tyrosine hydroxylase (TH), glutamic acid decarboxylase, choline acetyltransferase, glutamine synthetase (GS), neuron specific and non-neuronal enolase and 2',3'-cyclic nucleotide phosphohydrolase (CNP] as indices of neurotoxicity, changes in their activities were monitored after rats were treated with two doses of the neurotoxic agent, methylmercury chloride (MMC). Comparisons were also made of any histopathological changes occurring in the tissues examined. At the low dose rate (3.36 mg Hg/kg, po, for 14 days), the rats exhibited less body weight gain compared to untreated animals. No change in either the neuronal or noneuronal enzyme markers was observed in brain but a significant increase in the myelin marker, CNP, and total enolase activity was seen in the optic nerve. Morphological evaluation by light microscopy indicated no discernible neuronal lesions in MMC-exposed animals. At the higher MMC dose (7.05 mg Hg/kg, po, for 7 days), there was about a 20% loss in the body weight of treated animals and partial hind limb paralysis was observed. Of all the neuronal marker enzymes examined, only TH was found to be decreased in the striatum. The proliferating astroglial marker, GS, was elevated only in the cerebellum. CNP was found to be decreased in both the optic and sciatic nerve. As in the lower dose group no pathological changes were observed at the light microscopic level in the brain of MMC-treated rats. These data suggest that of the cell specific marker enzymes studied, GS in the cerebellum and TH in the striatum may be useful biochemical markers for the neurotoxic action of MMC.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1989

Effect of chronic exposure to hexachlorophene on rat brain cell specific marker enzymes.

The neurotoxicity associated with chronic exposure to hexachlorophene (HCP) was evaluated by measuring the activity of seven cell specific marker enzymes in brain and by comparing these measurements to morphological changes analyzed by light microscopy. Animals were divided into two groups, the experimental group received HCP at a daily dose of 20 mg/kg p.o. for 53 consecutive days whereas the control group received an equivalent amount of the vehicle only. HCP produced no change in the rate of gain in body weight nor did it produce a statistically significant change in brain weight. Furthermore, no overt abnormal neurological symptoms were observed at this level of exposure to HCP. The white matter throughout the brain was extensively vacuolated in the HCP-treated rats, imparting a spongiform structure which was absent in the white matter of the control animal brains. The data obtained reveal that chronic HCP treatment produce little change in any of the neuronal marker enzymes with the exception of a significant decrease in tyrosine hydroxylase activity in the striatum. Of the nonneuronal enzymes assayed, a significant increase in non-neuronal enolase, glutamine synthetase, and 2',3'-cyclic nucleotide phosphohydrolase was observed in the sciatic nerve, hippocampus and optic nerve, respectively.

Animals↗
PubMed1988

Qualitative and quantitative differences in the induction and inhibition of hepatic benzo[a]pyrene metabolism in the rat and hamster.

The present study compared the induction and inhibition of the metabolism of the prototype polycyclic aromatic hydrocarbon, benzo[a]pyrene (BaP), in rat and hamster liver microsomes. The production of total polar metabolites was quantitated by separating 3H-metabolites from [3H]-BaP using reverse-phase thin-layer chromatography. The rate of hepatic microsomal BaP metabolism was similar in the rat and hamster (0.81 vs 0.72 nmol/min/nmol cytochrome P-450 respectively). In the rat, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; 5 micrograms/kg, i.p.) and 3-methylcholanthrene (3-MC; 50 mg/kg, i.p., X 3 days) pretreatments doubled the rate of BaP metabolism, whereas phenobarbital pretreatment (PB; 80 mg/kg, i.p., X 3 days) had no effect. In contrast, hamster hepatic microsomal BaP metabolism was elevated 2.3-fold by PB pretreatment, whereas TCDD and 3-MC pretreatments had no effect. Isosafrole pretreatment (ISO; 150 mg/kg, i.p., X 3 days) elevated the rate by almost 2-fold in each species. Another cytochrome P-448-mediated activity, 7-ethoxyresorufin O-deethylase (EROD), was induced by the same compounds that induced BaP metabolism in the rat. In hamster liver microsomes, in contrast to BaP metabolism, EROD was induced by TCDD and 3-MC but not PB or ISO pretreatments. The results suggest differences in the substrate specificity of the cytochromes P-448-450 induced by TCDD, 3-MC and PB in these species. This was supported by the different selectivity of the in vitro inhibitors, metyrapone and 7,8-benzoflavone, towards BaP metabolism and EROD in hepatic microsomes from TCDD- or PB-pretreated rats and hamsters. Reverse-phase HPLC analysis indicated that, while 3-hydroxy-BaP was the major metabolite formed by the untreated rat, untreated hamster liver microsomes formed predominantly BaP-4,5-diol. Microsomes from TCDD-treated rats generated elevated levels of all BaP-diols, diones and 3-hydroxy-BaP, with the major metabolites being BaP-9,10- and BaP-7,8-diols. In contrast, the metabolite profile from TCDD-pretreated hamsters was unchanged from the control. PB-treated hamster microsomes produced elevated levels of BaP-diones and 3-hydroxy-BaP. However, the major hepatic metabolite formed by PB-pretreated hamsters was BaP-4,5-diol, while BaP-9,10- and BaP-7,8-diols were not detected. The results of the study indicate differences in the induced cytochrome P-450s and the generation of toxic BaP metabolites in the liver of the rat and hamster.

Animals↗
PubMed1988

Monoclonal antibodies to denatured ragweed pollen allergen Amb a I: characterization, specificity for the denatured allergen, and utilization for the isolation of immunogenic peptides of Amb a I.

The epitope structure of short ragweed allergen Amb a I (formerly antigen E or AgE) has been investigated by characterizing monoclonal antibodies (MAbs) from mice immunized with Amb a I. The MAbs to Amb a I that we previously produced and characterized (HaA1, HaB1 and HaC1) reacted with determinants which were conformationally dependent. Denaturation of Amb a I, which is a prerequisite for peptide isolation and hence epitope localization, destroyed these determinants. We report here the isolation of 15 MAbs produced against denatured Amb a I and present their reactivities with native Amb a I, denatured Amb a I, and peptide fragments of Amb a I. None of the 15 MAbs to denatured Amb a I bind to native Amb a I, as judged by their lack of binding to Amb a I in immune complex with HaA1 and HaC1. All 15 MAbs reacted with the extensively reduced and alkylated form of denatured Amb a I and 14 of the 15 were shown by Western blotting techniques and ELISA to have activity against the isolated alpha chain or beta chains of Amb a I, but not both. In addition, several MAbs react with tryptic fragments of Amb a I which allowed us to isolate and sequence two tryptic peptides of Amb a I. Antisera raised against KLH-coupled synthetic analogs of these peptides reacted well with intact, denatured Amb a I. Finally, during chromatographic purification of Amb a I from fresh pollen extracts, various MAbs began to react with Amb a I as a function of stage of isolation, suggesting that some proportion of Amb a I spontaneously denatures during purification, converting from the allergenic form possessing two major B cell epitopes to an allergenically inactive form.

Allergens↗
PubMed1988

Effect of short-term exposure to hexachlorophene on rat brain cell specific marker enzymes.

Seven cell specific marker enzymes in brain and optic nerve and morphological evaluation by light microscopy were used to characterize the neurotoxicity associated with exposure of rats to hexachlorophene (HCP; 40 mg/kg/day, po, for 9 days). In vitro exposure to HCP at concentrations up to 100 microM had no direct inhibitory effect on the marker enzymes, validating their use in evaluating brain function in vivo. Rats exhibited a reduction in body weight gain, weakness, and ataxia of the hind limbs by the ninth day of HCP exposure. At 24 hr following the last day of exposure to HCP, the activities of the three neuron specific enzymes, glutamic acid decarboxylase, tyrosine hydroxylase, and choline acetyltransferase, in rat brain were unchanged from those of the vehicle-treated control group. Of the two astroglial enzyme markers measured, a small but significant increase was observed in the activity of nonneuronal enolase in the cerebellum and glutamine synthetase in the hippocampus of HCP-treated rats. The optic nerve appeared to be the most sensitive tissue in that the activity of both the astroglial marker, nonneuronal enolase, and the myelin marker, 2',3'-cyclic nucleotide phosphohydrolase, was significantly decreased following HCP exposure. This decrease in enzyme activity is consistent with the histological observations demonstrating extensive vacuolization and edema in the optic nerve after exposure to HCP.

Animals↗
PubMed1988

Species differences in 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity and biotransformation in fish.

Rainbow trout, yellow perch, carp, bluegill, largemouth bass, and bullhead were treated with graded doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; 1, 5, 25, or 125 micrograms/kg) or vehicle, ip. The lethal potency of TCDD tended to be greater in yellow perch, carp, and bullhead than in the other three species (LD50 80 days post-treatment, 3-5 versus 10-16 micrograms/kg, respectively). All species treated with the highest dose of TCDD (125 micrograms/kg) displayed a latency period of 1-4 weeks prior to death; longer latency periods were produced by lower lethal doses. Effects of TCDD treatment on body weight were both species-dependent and dose-dependent. Fin necrosis was observed in all fish species; however, cutaneous hemorrhage was observed only in TCDD-treated perch, carp, and bluegill, and cutaneous hyperpigmentation only in TCDD-treated carp and largemouth bass. Gallbladder bile was analyzed for TCDD and its metabolites 7 days after fish were injected with [14C]TCDD (60 micrograms/kg, ip). At least three TCDD metabolites in addition to the parent compound were found in the gallbladder bile of all six species. In addition, the retention time of the major biliary TCDD metabolite (determined by HPLC) was similar in all species except yellow perch. Beta-Glucuronidase treatment of the bile from largemouth bass and bluegill suggested that at least two of the TCDD metabolites were glucuronide conjugates. Thus, species differences exist in the lethal potency, signs of overt toxicity, and biotransformation of TCDD among freshwater fish.

Animals↗
PubMed1986

Metabolism and disposition of 2,3,7,8-tetrachlorodibenzo-p-dioxin in guinea pigs.

Marked interspecies variability exists in the acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), with the guinea pig being the mammalian species most sensitive to the acute toxicity of TCDD. The metabolism and disposition of TCDD was investigated in guinea pigs for 45 days following a single exposure to purified [3H]TCDD (0.56 microgram/kg, ip). Guinea pigs included in the toxicokinetic study gained body weight, maintained a normal relative body composition, and exhibited no gross signs of toxicity during the 45-day study. Approximately 36% of the dose of TCDD-derived 3H remained in the adipose tissue at 45 days following exposure to [3H]TCDD, while the liver, pelt, and skeletal muscle and carcass each contained about 7% of the administered dose. Although most of the TCDD-derived radioactivity in liver, kidney, perirenal adipose tissue, and skeletal muscle represented unchanged TCDD, from 4 to 28% of the 3H was associated with metabolites of TCDD. This unexpected finding suggests that TCDD metabolites are not efficiently excreted from guinea pigs. The urinary and fecal excretion of TCDD-derived radioactivity followed apparent first-order kinetics, with an elimination half-life of 93.7 +/- 15.5 days (mean +/- SD). HPLC analysis of urine and bile from [3H]TCDD-treated guinea pigs showed that all of the radioactivity represented metabolites of TCDD, indicating that these routes of elimination are dependent on prior metabolism of TCDD. However, 70 to 90% of the radioactivity in fecal samples was found to represent unmetabolized TCDD throughout the 45-day excretion study. The presence of TCDD in feces and its absence in bile suggest that the fecal excretion of unchanged TCDD resulted from the direct intestinal elimination of the lipophilic toxin. Furthermore, the cumulative excretion of TCDD-derived radioactivity over 45 days indicated that 74.3% of the 3H was excreted in feces as unchanged TCDD, while 25.7% of the 3H was excreted in urine and feces as TCDD metabolites. Thus, TCDD is primarily eliminated unchanged in the feces of guinea pigs, indicating that the metabolism of TCDD does not play a major role in the ultimate elimination of the toxin from the guinea pig. This may in part explain the relatively long excretion half-life for TCDD in the guinea pig and may contribute to the remarkable sensitivity of the guinea pig to the acute toxicity of TCDD.

Animals↗
PubMed1986

Two major human allergenic sites on ragweed pollen allergen antigen E identified by using monoclonal antibodies.

Murine monoclonal antibodies specific for antigen E (AgE), the major allergen isolated from short ragweed pollen, have been produced and characterized. These monoclonal antibodies, when coupled to Sepharose and used as immunoadsorbents, specifically bound AgE when a crude pollen extract was passed through the column. Three antigenic sites (A, B, and C) on AgE were identified by using five of these monoclonal antibodies in both inhibition and double-bind solid-phase ELISA. These three antigenic sites appear to be nonoverlapping and nonrepeated, that is, present only once on each AgE molecule. Site C on AgE could readily be bound by the monoclonal antibody specific for that site, but only when AgE was in solution or "presented" by an anti-site A or anti-site B antibody. Site C appears to be only marginally available for binding when AgE is directly adsorbed to polyvinyl chloride microtiter wells. The majority of monoclonal antibodies isolated after immunization of BALB/c mice were specific for site A on AgE. In addition, the binding to AgE of pooled BALB/c polyclonal, hyperimmune antisera against AgE was blocked approximately 80% by a monoclonal antibody directed against site A, but was only blocked approximately 20% by an anti-site B monoclonal antibody. This suggests that site A on AgE is the predominant antigenic site in the BALB/c immune response and that site B represents a less dominant site. The binding of IgE in pooled human serum from ragweed-allergic individuals is blocked approximately 50% by a monoclonal antibody directed to site A on AgE and also approximately 50% by a monoclonal antibody directed against site B. A series of individual human short ragweed allergic antisera also showed significant, although varied, inhibition of IgE binding to AgE by both anti-site A and anti-site B monoclonal antibodies. Simultaneous addition of anti-site A and anti-site B was somewhat additive and inhibited up to 80% of the binding of human IgE specific for AgE. The conclusion from these data is that site A and site B defined by two murine monoclonal antibodies represent two very major allergenic sites in the human response to this molecule.

Allergens↗
PubMed1986

Metabolism and disposition of 2,3,7,8-tetrachlorodibenzo-p-dioxin in rainbow trout.

Accumulation, tissue distribution, and depuration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-derived 3H were studied in fingerling rainbow trout fed a diet containing 494 ppt [3H]TCDD for 13 weeks followed by the same diet without TCDD for 13 weeks. This exposure did not cause fin rot, cutaneous hemorrhage, reduced growth rate, or an increase in relative lethality in TCDD-exposed fish. Visceral fat, carcass, skin, and pyloric caeca and all fatty tissues, accounted for greater than 90% of the TCDD-derived 3H in the fish after the 13-week exposure period. The remaining TCDD-derived radioactivity was distributed to skeletal muscle, gill, gastrointestinal tract, liver, kidney, heart, and spleen. High-pressure liquid chromatographic analysis of 3H in skeletal muscle, liver, kidney, carcass, and visceral fat showed that it was primarily due to TCDD (greater than or equal to 98%) and not metabolites (less than or equal to 2%). The t1/2 for whole-body depuration of TCDD-derived 3H was 15 weeks, and individual organ t1/2 values ranged from 8 to 19 weeks. To determine if rainbow trout metabolize TCDD, adult fish were injected with [14C]TCDD (60 micrograms/kg, ip), and gallbladder bile, liver, skeletal muscle, and kidney were analyzed 1 week later. While only the parent compound was found in the tissues, bile contained at least three TCDD metabolites and the parent compound. beta-Glucuronidase treatment of the bile suggested that at least one TCDD metabolite was a glucuronide conjugate.

Animals↗
PubMed1986

2,3,7,8-Tetrachlorodibenzo-p-dioxin metabolism and disposition in yellow perch.

Accumulation, tissue distribution, and depuration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-derived 3H were examined in fingerling yellow perch fed a diet containing 494 ppt of [3H]TCDD for 13 weeks followed by the same diet without TCDD for 13 weeks. None of the TCDD-exposed perch showed any signs of overt toxicity such as reduced growth rate, fin necrosis, cutaneous hemorrhage, or lethality. At the end of the 13-week exposure period, 78% of the total body burden of TCDD-derived 3H was contained in the carcass and visceral fat while the remaining 22% was distributed among the liver (9%), gill (5%), skin (3%), skeletal muscle (2%), gastrointestinal tract (1%), pyloric caeca (1%), kidney (less than 1%), spleen (less than 1%), and heart (less than 1%). High-performance liquid chromatographic analysis of organic extracts of visceral fat, carcass, liver, skeletal muscle, and skin showed that 96-99% of the tritium extracted from these tissues was due to the parent compound. The estimated t1/2 for whole-body depuration of TCDD-derived 3H was 18 weeks, and individual organ t1/2 values ranged from 6 to 19 weeks for the gastrointestinal tract, pyloric caeca, liver, gill, and carcass, and from 24 to 49 weeks for the visceral fat, kidney, skin, skeletal muscle, and spleen. To determine if yellow perch metabolize TCDD, a single dose of [14C]TCDD was administered to adult yellow perch (60 micrograms/kg, ip), and, 1 week later, gallbladder bile, liver, skeletal muscle, and kidney were removed, extracted, and analyzed by high-performance liquid chromatography. In contrast to the liver, muscle, and kidney where the parent compound accounted for 96-99% of the extractable 14C, the gallbladder bile contained almost entirely TCDD metabolites. At least four TCDD metabolites were detected in yellow perch bile and beta-glucuronidase treatment of the bile suggested that at least one was a glucuronide conjugate.

Adipose Tissue↗
PubMed1986

Distribution of the thrombomodulin antigen in the rabbit vasculature.

The purpose of this study was to determine the distribution of the thrombomodulin (TM) antigen in the rabbit vasculature in vivo. Acetone-fixed, frozen sections of various tissues (brain, heart, aorta, lung, liver, spleen, kidney, small intestine, large intestine, skeletal muscle, bone, and skin) were stained by indirect immunofluorescence with goat affinity-purified antibodies to TM. Both large and small vessels (including capillaries) had demonstrable TM antigen localized to the endothelium while vascular smooth muscle and connective tissue cells were negative. The parenchyma of the organs examined were also negative. Based on antibody dilutions and brightness of staining, there is an indication that lung, followed by heart and intestinal vessels, has the highest concentration of antigen; kidney glomerular capillary loops have the least. These results also indicate that TM is an excellent cell type-specific marker of endothelial cells as the endothelium of all vessels and vascular beds was positive.

Animals↗
PubMed1985

Hepatic metabolism of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the rat and guinea pig.

Marked interspecies variability exists in the acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), with the rat having an LD50 about 25-fold greater than the guinea pig. The metabolism of TCDD was examined by incubating hepatocytes isolated from these animals with purified [14C]TCDD (2.2 microM) for 8 hr. Over the 8-hr incubation, cytochrome P-450 content and ethoxyresorufin O-deethylase and benzphetamine N-demethylase activities were well maintained, indicating the functional viability of the hepatocytes. Quantitative differences were observed in the rate of [14C]TCDD metabolism, with hepatocytes from control rats metabolizing TCDD at a rate 2.8-fold greater than hepatocytes from control guinea pigs. The role of the hepatic cytochrome P-450-448-dependent monooxygenase system in the metabolism of TCDD was examined through the use of hepatocytes isolated from animals pretreated with either TCDD (5 micrograms/kg, ip; 72 hr prior to hepatocyte isolation) or phenobarbital (80 mg/kg, ip X 3 days; 24 hr prior to isolation). The rate of [14C]TCDD metabolite formation in hepatocytes from TCDD pretreated guinea pigs (0.26 +/- 0.14 pmol mg cell protein-1 hr-1) was unchanged from the control rate (0.25 +/- 0.07), while the rate in hepatocytes from TCDD pretreated rats (2.26 +/- 0.43 pmol mg-1 hr-1) was 3.2-fold greater than control (0.70 +/- 0.10) and nine times greater than in hepatocytes from TCDD-pretreated guinea pigs. In addition, significant differences were observed in the profiles of the metabolites formed by hepatocytes from TCDD-pretreated rats and guinea pigs. On the other hand, phenobarbital pretreatment produced little change in the rate of [14C]TCDD metabolism in rat hepatocytes (0.98 +/- 0.13 pmol mg-1 hr-1). These results suggest that TCDD may be metabolized by a TCDD inducible form of cytochrome P-448 which is expressed in the rat but not in the guinea pig. Furthermore, the differences in the hepatic metabolism of TCDD in the rat and guinea pig and in the ability of TCDD to induce its own rate of metabolism may play a major role in explaining the varying susceptibility of these species to the acute toxicity of TCDD.

Animals↗