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Biomedical subjects

M E Hahn

Publications and source records attributed to M E Hahn.

At least 55 records · Page 3Linked to original sources
PubMed1995

Induction of cytochrome P4501A1 by aryl hydrocarbon receptor agonists in porcine aorta endothelial cells in culture and cytochrome P4501A1 activity in intact cells.

Endothelium is a single-cell layer lining blood vessels and constituting capillaries and could be a primary site of chemical effects in the cardiovasculature and systemically. Cytochrome P4501A1 (CYP1A1) is strongly inducible in vertebrate endothelium in vivo by aryl hydrocarbon receptor (AhR) agonists [Mol. Pharmacol. 36:723-729 (1989); Mol. Pharmacol. 41:1039-1046 (1992)]. We investigated CYP1A expression and activity in porcine aorta endothelial cells (PAEC) exposed in culture to the AhR agonists 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3,3',4,4'-tetrachlorobiphenyl (TCB), benzo[a]pyrene (BP), or beta-naphthoflavone (BNF). Immunoblotting with monoclonal anti-CYP1A1 and polyclonal anti-CYP1A1 and anti-CYP1A2 antibodies showed that CYP1A1 was induced in cultures exposed to TCDD, TCB, BP, or BNF but was not detectable in untreated or dimethylsulfoxide-exposed cultures. CYP1A1 was strongly induced at intermediate concentrations (0.1 microM or 1.0 microM) of TCB, BP, or BNF, but induction was suppressed by higher concentrations, a response not due to general toxicity; cell viability (trypan blue exclusion) was > 97% with BNF or TCB at up to 10 microM. CYP1A1 induction by TCDD was maximal at 0.3-1.0 nM. ED50 values for induction of CYP1A1 by TCDD, TCB, and BP were 0.016 nM, 3-10 nM, and 180 nM, respectively. Immunohistochemical analysis confirmed CYP1A1 induction in PAEC but also showed that only some cells in the cultures were induced. Subcellular fractionation, marker enzyme analysis, and immunoblot analysis showed that PAEC had a typical complement of microsomal electron-transport components. NADPH-cytochrome P450 reductase showed comparable rates (approximately 40 nmol/min/mg) in induced and control cultures. Cultures maximally induced by 0.1 microM TCB had microsomal CYP1A1 [ethoxyresorufin-O-deethylase (EROD)] activity averaging 25 pmol/min/mg. Addition of purified rat reductase to PAEC microsomes increased the EROD rates 3-fold. EROD rates measured in intact cells maximally induced by BP, TCB, or TCDD ranged from 15 to 30 pmol/min/mg of whole-cell protein. Methoxyresorufin O-demethylase activity induced by TCDD was 2 pmol/min/mg, i.e., < 10% of the EROD activity. In cultures in which CYP1A1 was strongly induced, CYP1A2 was not detectably expressed. The CYP1A2 inducer acenaphthylene did not induce EROD or methoxyresorufin O-demethylase in intact cells. The results show that CYP1A1 but not CYP1A2 is strongly induced in mammalian endothelial cells in culture and that CYP1A1 is active in intact cells, although the catalytic rates are low.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Photoaffinity labeling of the Ah receptor: phylogenetic survey of diverse vertebrate and invertebrate species.

The mammalian aromatic hydrocarbon (Ah) receptor is a soluble protein involved in the regulation of gene expression by halogenated aromatic hydrocarbons such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Little is known, however, about the presence and properties of this receptor in nonmammalian species. In these studies, we sought evidence for an Ah receptor in the liver or liver-equivalent of diverse species of invertebrate and vertebrate animals. Velocity sedimentation analysis of hepatic cytosol labeled with [3H]TCDD gave equivocal results with three species of marine fish. In subsequent studies, photoaffinity labeling with 2-azido-3-[125I]iodo-7,8-dibromodibenzo-p-dioxin was used to identify the Ah receptor. Specific labeling (labeling that could be displaced by an excess of unlabeled ligand) was observed in seven species of teleost and elasmobranch fish, including winter flounder (Pleuronectes americanus), killifish (Fundulus heteroclitus), scup (Stenotomus chrysops), rainbow trout (Oncorhynchus mykiss), brown trout (Salmo trutta), and dogfish (Mustelus canis and Squalus acanthias). Specific labeling was also found in cytosolic fractions prepared from PLHC-1 fish hepatoma cells and livers of a turtle (Chrysemys picta) and a cetacean, the beluga whale Delphinapterus leucas. The fish Ah receptor was sensitive to conditions of tissue preparation; inclusion of proteinase inhibitors in the homogenization buffer stabilized the receptor in some species. There was heterogeneity in the apparent molecular mass of the largest specifically labeled band in each species; these ranged from 105 to 146 kDa, slightly larger on average than mammalian Ah receptors (95-130 kDa). In contrast to the results obtained with teleost and elasmobranch fish, no specifically labeled polypeptides were detectable in cytosol from two agnathan fish species (hagfish Myxine glutinosa and sea lamprey Petromyzon marinus), the tunicate Ciona intestinalis, or any of nine other invertebrate species representing eight classes in four phyla. Overall these results suggest that the Ah receptor evolved at least 450 million years ago, prior to the divergence of bony and cartilaginous fishes. Although the exact relationship between receptor presence and dioxin responsiveness in these species is uncertain, our data predict that the invertebrate species examined in this study, which appear to lack an Ah receptor protein like that seen in mammals and fish, may be less sensitive than vertebrates to the effects of environmental contaminants that act through this transcriptional regulator.

Affinity Labels↗
PubMed1994

Catalytic and immunochemical characterization of hepatic microsomal cytochromes P450 in beluga whale (Delphinapterus leucas).

Understanding the effects of environmental contaminants on cetaceans and other marine mammals will require information on the biochemistry of xenobiotic metabolism in these species. We characterized the hepatic microsomal cytochrome P450 system in beluga whales (Delphinapterus leucas) from the Canadian Arctic. The content of native P450 averaged 0.203 and 0.319 nmol/mg microsomal protein, cytochrome b5 content averaged 0.199 and 0.236 nmol/mg, and rates of NADPH-cytochrome c reductase were 79 and 76 nmol/min/mg, for females and males respectively. Ethoxyresorufin O-deethylase (EROD), pentoxyresorufin O-depentylase (PROD), and benzo[a]pyrene (BP) hydroxylase (AHH) activities were significantly greater in males than in females, and were highly correlated with one another (r2 between 0.853 and 0.912). HPLC analysis of in vitro BP metabolites revealed benzo-ring (7,8- and 9,10-) dihydrodiols, consistent with activation of this compound, as well as 4,5-dihydrodiol,3-OH-, 7-OH-, and 9-OH-BP and 1,6- and 3,6-quinones. Estradiol 2-hydroxylase activity did not differ between sexes, and rates did not correlate with those of the other activities. Antibodies against scup P450B (an apparent teleost CYP2B) and rat CYP2B1 did not recognize proteins in beluga liver microsomes, but there was a protein detected by antibodies to PB-inducible rabbit CYP2B4. Antibodies to ethanol and ketone-inducible rat CYP2E1 reacted with two proteins in beluga liver microsomes. Antibodies specific to hydrocarbon-inducible CYP1A1 and/or CYP1A2 forms showed a single protein band, apparently more closely related to CYP1A1. The content of CYP1A was fivefold greater in male than in female beluga. CYP1A content was highly correlated with EROD, PROD, and AHH activities, suggesting that this P450 form is a primary catalyst for these reactions in beluga. CYP1A content and activity were highly correlated with the concentrations in blubber of non-ortho and mono-ortho PCB congeners, compounds that induce CYP1A in other mammals. These results indicate that a CYP1A is a catalyst for the metabolism of aromatic hydrocarbon pollutants in the beluga whale, and strongly suggest that this protein is induced in these organisms by environmental contaminants, including PCBs. The results support the measurement of CYP1A expression as a biomarker of exposure to inducers in marine mammals. The full functional and evolutionary relationships of beluga CYP1A and of beluga proteins immunologically related to other P450 forms are uncertain.

Animals↗
PubMed1994

Regulation of cytochrome P4501A1 in teleosts: sustained induction of CYP1A1 mRNA, protein, and catalytic activity by 2,3,7,8-tetrachlorodibenzofuran in the marine fish Stenotomus chrysops.

Cytochrome P4501A1 (CYP1A1) is known to play important roles in the activation and detoxification of carcinogens and other toxicants in vertebrate animals, including fish. Although extensively studied in mammalian systems, the regulation of CYP1A forms in other vertebrates is less well understood. We examined the time course and dose-response relationships for induction of CYP1A1 mRNA, protein, and catalytic activity by 2,3,7,8-tetrachlorodibenzofuran (TCDF) in the marine fish Stenotomus chrysops (scup). The time course of CYP1A1 induction was determined following a single ip dose (10 nmol/kg) of 2,3,7,8-TCDF. Hepatic ethoxyresorufin O-deethylase activity was increased after 1 day, reached a maximum by 8 days, and was still elevated 14 days after treatment. The content of immunodetectable CYP1A1 protein in liver was elevated on Day 1 and continued to increase through 14 days. CYP1A1 protein content was also strongly induced in heart and gill beginning at 2 days after treatment and extending through Day 14. Hepatic CYP1A1 mRNA was strongly induced by 1 day after dosing and remained elevated through 14 days. The sustained induction of CYP1A1 mRNA by 2,3,7,8-TCDF contrasts with the transient induction seen previously in fish treated with nonhalogenated inducers and most likely reflects differences in persistence of the inducers. Dose-response studies indicated that induction of CYP1A1 mRNA, protein, and catalytic activity occurred following doses of 2,3,7,8-TCDF as low as 0.4 nmol/kg (120 ng/kg), within the range of whole-body contents of this congener measured in fish from contaminated environments. The estimated dose producing half-maximal CYP1A1 induction in scup was approximately 2-10 nmol/kg, suggesting that the sensitivity of these fish to induction may be as great as or greater than that of rats. In contrast to previous results obtained with 3,3',4,4'-tetrachlorobiphenyl (TCB) and beta-naphthoflavone, which appear to inhibit or inactivate CYP1A1 in fish and other vertebrates, there was a good correlation among levels of CYP1A1 mRNA, protein, and catalytic activity in individual fish following various doses of 2,3,7,8-TCDF. The difference in response to 2,3,7,8-TCDF versus 3,3',4,4'-TCB may reflect differences in the inducing potencies of the two compounds relative to their similar potencies as inhibitors of CYP1A1 catalytic activity. In additional studies to evaluate structure-activity relationships for CYP1A1 induction by chlorinated dibenzofurans in fish, scup were treated with 2,3,6,8-tetrachlorodibenzofuran (2,3,6,8-TCDF). At 10 or 50 nmol/kg, 2,3,6,8-TCDF was inactive as an inducer of CYP1A1 mRNA, protein, or catalytic activity.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Immunohistochemical localization of environmentally induced cytochrome P450IA1 in multiple organs of the marine teleost Stenotomus chrysops (Scup).

Differences in expression of cytochrome P450 forms and their functions in different organs and cell types could determine the response of those cells and organs to xenobiotics. Recently, we described the cellular localization of cytochrome P450IA1 (P450E) induced in 10 organs or organ systems of the fish, Stenotomus chrysops (scup) treated with 3,3',4,4'-tetrachlorobiphenyl or with 2,3,7,8-tetrachlorodibenzofuran. (R.M. Smolowitz, M.E. Hahn, and J.J. Stegeman, Drug Metab. Dispos. 19, 113, 1991). Here we describe the presence and localization of P450IA1 in organs of scup sampled directly from an environment contaminated by chlorinated biphenyls and bibenzofurans, the outer New Bedford Harbor of Massachusetts. Western blot analysis of microsomes from selected organs (liver, kidney, gill, and heart), using monoclonal antibody 1-12-3, revealed induced levels of P450IA1 in each. The localization of P450IA1 in these and other organs was determined in sections prepared by standard histological methods and stained with MAb 1-12-3 in an indirect peroxidase labeling method. P450IA1 was detected in multiple cell types in liver, including hepatic, pancreatic, and vascular tissue. Kidney and gut also showed prominent P450IA1 levels in epithelial structures and in vascular endothelial cells. Specific staining was detected in endothelial cells, but not other cell types, in heart, gill, spleen, testis, ovary, nose, and brain. In heart, the staining was present in the endocardium of atrium and ventricle, and endothelium of the coronary vasculature and great vessels. The results demonstrate that P450IA proteins are induced in many organs of fish exposed to environmental chemicals in the wild, with patterns of cellular localization like those seen in fish experimentally treated with known inducers. The strong staining of P450IA1 in endothelial cells in all organs examined supports experimental results indicating that endothelium is a major site of P450IA1 induction. Our results indicate further that immunohistochemistry is a useful method for detecting P450 induction as a biomarker for exposure.

Animals↗
PubMed1991

Determination of individual porphyrins in rodent urine using high-performance liquid chromatography following clean-up by anion-exchange chromatography.

We describe a method for the rapid clean-up of rodent urine samples prior to the analysis of porphyrin carboxylic acids by reversed-phase high-performance liquid chromatography (HPLC) with fluorescence detection. A simple pretreatment step using chromatography on a Dowex 1X8 anion-exchange resin effectively removes fluorescent substances that are present in rodent urine and would otherwise interfere with the detection and quantitation of urinary porphyrins by HPLC. Recovery of porphyrins with four to eight carboxyl groups (coproporphyrin to uroporphyrin) averaged 93% using this procedure. The use of this method to determine the amount of individual porphyrins present in the urine of hexachlorobenzene-treated mice is illustrated.

Animals↗
PubMed1991

Genetic analysis of cerebellar foliation patterns in mice (Mus musculus).

Four inbred strains of mice, DBA/2J, C57BL/10J, BALB/cJ, and SJL/J, were mated in a diallel cross. The cerebella of the F1 generation were examined for the presence (Type I) or absence (Type II) of an intraculminate fissure between vermian lobule IV and vermian lobule V (the ventral and dorsal lobules of the culmen). One strain (DBA/2J) consistently expressed the Type I pattern. Another strain (SJL/J) expressed predominantly the Type II pattern. The other two strains (C57BL/10J and BALB/cJ) and many of the hybrids exhibited variability in their expression of the foliation patterns. The results were analyzed using biometrical genetic procedures and showed significant additive and dominance genetic effects and a maternal effect. Correlations of these cerebellar anatomical variants with the development of behavior are discussed.

Animals↗
PubMed1991

Lead effects on food competition and predatory aggression in Binghamton HET mice.

The ubiquity of lead in our environment, its toxic nature and its potential to alter behavior of humans and animals has stimulated much research. In addition to the well known, but complex, changes in activity and performance of learned tasks following exposure to lead, an increasing body of literature suggests that changes in social behavior also occur. This study examined the impact of ingesting a 0.5% lead acetate solution (as the only available fluid)--a protocol that results in ca. 100 micrograms/dl blood-levels in our Binghamton Heterogenous (HET) mice--on food competition in both male and female HET mice. Effects of this lead exposure on cricket predation by the same HET mice also were observed. Our results from the food competition study (Experiment I) show, compared with water controls, that such exposure to lead increases both food possession time and amount of social contact after food consumption; but very little agonistic behavior took place in either the water control or lead-exposed competition testing sessions. In the cricket predation observations (Experiment II) there was a tendency for lead exposure to reduce the latency of males to attack, and the indication that lead-exposed females initially attacked a cricket's legs more often than any of the other groups. In fact, suggestions of such gender x treatment interactions occurred in both the food competition and the predation work. Overall, we believe our results, in conjunction with other relevant literature, suggest that exposure to lead reduced the individual's general fitness, even when levels are relatively low.

Aggression↗
PubMed1991

Genetic analyses of the biphasic nature of the alcohol dose-response curve.

Ethanol (ETOH)-induced locomotor activation and depression were studied in 23 genotypes of mice. This included a diallel cross of four inbred strains tested with a range of ETOH doses from 0 to 2.75 g/kg. The diversity in shapes of the biphasic ETOH dose-response curves was both qualitative and quantitative, and additive gene action characterized the genetic control of the dose-response curve. Small dominance effects were typically directional in the direction of more activation, or resistance to sedation. No evidence was found for maternal effects, sex linkage, or epistasis. Sex differences were seen in the increased susceptibility of male mice to locomotor sedation at higher ETOH doses. In the diallel cross, there was no correlation between the degree of activation produced by low ETOH doses and sedation produced by higher doses. This indicates that while considerable genetic influences exist for both activational and sedative domains of ETOH effects, these genetic influences are relatively independent.

Adult↗
PubMed1989

Interaction of hexachlorobenzene with the receptor for 2,3,7,8-tetrachlorodibenzo-p-dioxin in vitro and in vivo. Evidence that hexachlorobenzene is a weak Ah receptor agonist.

Hexachlorobenzene (HCB) produces hepatic porphyria and induces the hepatic cytochrome P450 isozymes P450c (P450IA1) and P450d (P450IA2) in rodents. These and other effects of HCB resemble those of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), which acts via its binding to the aromatic hydrocarbon (Ah) receptor. We therefore examined the ability of HCB to interact with this receptor in vitro and in vivo. HCB, at concentrations of 1 microM or higher, inhibited the specific binding of [3H]TCDD (0.3 nM) to the Ah receptor in vitro, whereas the solubility of [3H]TCDD was affected only at 100 microM HCB. The inhibition was competitive, with a KI of approximately 2.1 microM. In rats fed a diet containing 3000 ppm HCB for varying times (4 h to 7 days), the specific binding of [3H]TCDD in hepatic cytosol was reduced by up to 40%, as observed previously for known Ah receptor agonists. The decrease in [3H]TCDD specific binding in cytosol of HCB-treated rats was due principally to a decrease in the number of binding sites for [3H]TCDD rather than competition from residual HCB. As shown by immunoblotting and radioimmunoassay, HCB induced the cytochrome P450 isozymes P450c and P450d, which are regulated by the Ah receptor, as well as the phenobarbital-inducible isozymes P450b and P450e. Together these results indicate that HCB is a weak agonist for the Ah receptor, and suggest that some of its effects may be mediated by its interaction with this gene-regulatory protein.

Animals↗
PubMed1989

Effects of ortho- and non-ortho-substituted polychlorinated biphenyl congeners on the hepatic monooxygenase system in scup (Stenotomus chrysops).

Polychlorinated biphenyl congeners that are abundant in environmental samples, and known to induce hepatic monooxygenase isozymes in the P450IA gene subfamily in mammals, were examined for their ability to induce hepatic monooxygenase activity in scup, a marine teleost. Scup were dosed ip with 3,3',4,4'-tetrachlorobiphenyl (congener 77), 2,3,3',4,4'-pentachlorobiphenyl (congener 105), 2,3',4,4',5-pentachlorobiphenyl (congener 118), 2,2',3,4,4',5'-hexachlorobiphenyl (congener 138), 2,2',3,3',4,4'-hexachlorobiphenyl (congener 128), or beta-naphthoflavone and examined for increases in ethoxyresorufin O-deethylase (EROD) activity, immunodetectable cytochrome P450E (the EROD catalyst in scup), and in vitro translatable mRNA for P450E. Monooxygenase parameters were significantly induced only by 3,3',4,4'-tetrachlorobiphenyl (TCB). However, while translatable mRNA for P450E was induced at all doses (1, 5, and 10 mg/kg), EROD activity and P450E were decreased at the 5 and 10 mg/kg doses, relative to the response at 1 mg/kg. A strong relationship between residual TCB concentration in the liver and the decreased EROD activity was evident at the higher doses of TCB. Aminopyrine N-demethylase, a monooxygenase activity not catalyzed by P450E, was unaffected by TCB treatment, indicating a specificity in the TCB effect. Analysis in vitro revealed that TCB was a potent competitive inhibitor of EROD activity, with half-maximal inhibition at 0.3 microM, near the Km for ethoxyresorufin, suggesting one mechanism for the in vivo effect of TCB. These results demonstrate that PCB congeners with ortho-chlorine substitution, and which are effective inducers of AHH and EROD activity in mammals, are ineffective, at the doses tested, as inducers in the teleost scup.

Animals↗
PubMed1988

The role of the Ah locus in hexachlorobenzene-induced porphyria. Studies in congenic C57BL/6J mice.

The role of the Ah locus in hexachlorobenzene (HCB)-induced porphyria and the possible involvement of P-450 cytochromes P(1)450 and P(3)450 in the pathogenesis of this disease were investigated in two congenic strains of C57BL/6J mice that differ only at this locus. Female B6-Ahb mice (Ah receptor: approximately 30-70 fmol/mg of cytosolic protein) and B6-Ahd mice (Ah receptor: undetectable) were pretreated with iron (500 mg/kg) and then fed a diet containing 0 or 200 p.p.m. of HCB for up to 17 weeks. Mice from the two strains consumed similar amounts of HCB. Urinary excretion of porphyrins was increased after 7 weeks of HCB treatment in B6-Ahb mice, and after 15 weeks was over 200 times greater than that of mice given iron only. In B6-Ahd mice, porphyrin excretion did not begin to increase until after 13 weeks, and after 15 weeks was only six times greater than that of controls. Similar differences were seen in the 15-week hepatic porphyrin concentrations (B6-Ahb: 1110 +/- 393; B6-Ahd: 17.6 +/- 14.5; controls: approximately 0.20 nmol/g). Uroporphyrinogen decarboxylase (EC 4.1.1.37) activity was diminished by 70 and 20% in B6-Ahb B6-Ahd mice respectively after 15 weeks of treatment with HCB. Cytochromes P(1)450 and P(3)450 were measured in hepatic microsomes (microsomal fractions) by radioimmunoassay and immunoblotting, using antisera raised against the orthologous rat isoenzymes P450c and P450d. HCB induced small amounts of a protein recognized by anti-P450c (P(1)450) in B6-Ahd mice, but not in B6-Ahd mice. Relatively large amounts of a protein recognized by anti-P450d (P(3)450) were induced in both strains, but to a somewhat greater extent in the B6-Ahb mice. The hepatic accumulation of HCB at 15 weeks was greater in B6-Ahb than in B6-Ahd mice, in association with elevated hepatic lipid levels in the former strain. The results of this experiment indicate that the Ah locus influences the susceptibility of C57BL/6J mice to HCB-induced porphyria and are consistent with the suggestion that the sustained induction of P(3)450 and/or P(1)450 may be a causative factor in the development of this disease.

Animals↗
PubMed1987

Genetic selection disrupts stability of mouse brain weight development.

Fuller Brain Weight Selection lines are well differentiated for 42-day brain weight and a high degree of genetic homogeneity for trait-relevant genes is indicated. Using these lines, random bred descendants of the foundation population and an inbred line, biometrical analysis of brain growth from birth to 23 days was attempted. While strain means differ as expected, within and between litter variances for genetically heterogeneous mice were typically no greater than for more genetically homogeneous selected lines. Possible explanations involving gestational age, intra-uterine and postnatal competition and ontogenetic buffering are discussed.

Aging↗
PubMed1986

Structure-activity relationships of chlorinated benzenes as inducers of hepatic cytochrome P-450 isozymes in the rat.

This study compared the ability of hexachlorobenzene (HCB) and of other chlorinated benzenes to induce cytochrome P-450 isozymes in rat liver. HCB (greater than 99% pure) induced both the phenobarbital-inducible forms (cytochrome P-450b and P-450e) and the 3-methylcholanthrene (3-MC)-inducible forms (P-450c and P-450d) of cytochrome P-450. However, HCB differed from many 3-MC-type inducers by inducing P-450d preferentially over P-450c. In contrast to HCB, the lower chlorinated benzenes did not induce significant amounts of P-450c or P-450d in the rat, but were phenobarbital-type inducers, inducing P-450b and P-450e. These data indicate that the hepatic effects of HCB differ markedly from those of other chlorinated benzenes. However, chlorinated dibenzodioxins also induce P-450c and P-450d in the rat, and although chlorinated dibenzodioxins and dibenzofurans contaminate certain commercial products, none were detected by gas chromatography/mass spectrometry (detection limit 0.5 ppm) in the HCB used in this study. The evidence that HCB interacted with the receptor for 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD) was equivocal. At a concentration of 10(-6) M, HCB produced a slight decrease (18%) in the binding of 3H-TCDD to this protein in vitro, but had no effect at lower concentrations. However, as an inducer of two 3-MC-inducible isozymes of P-450, HCB was clearly more effective in aromatic-hydrocarbon-responsive mice (C57Bl/6J) than in non-responsive mice (DBA/2J), suggesting that HCB may act through the Ah receptor.

Animals↗
PubMed1983

Brain growth in young mice: evidence on the theory of phrenoblysis.

Brain growth was studied from day of birth through 23 days of age in three outbred and one inbred groups of mice. The results showed that the brain grows rapidly from Birth through 11 days and quite slowly thereafter. We found no evidence of the several spurts and plateaus in growth that are central to the theory of phrenoblysis (correlated brain and mind growth). Our results show the main features of mouse brain growth to parallel those of human brain growth except for timing of rapid and slow growth.

Aging↗
PubMed1976

Issues in the genetics of social behavior.

The genetics of social behavior presents special difficulties because the phenotype is the product of an interaction between two or more individuals. Social interactions are of two kinds: (1) cooperative, in which the probabilities of transmission of the genes of all participants are similarly affected by the outcome, and (2) agonistic, in which the probabilities for the participants are affected in opposite directions. The latter are of particular interest for evolutionary theory. Three major types of designs for measuring social behavior in genetic experiments are available: (1) homogeneous sets, (2) standard tester, and (3) tester panel representing a reference population. The advantages and limitations of each method are discussed. Important areas for future development include the relationship of genetic and experiential factors in early life to social status as an adult and the extension of the genetic analysis of social behavior to natural populations.

Animals↗