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S Matsuda

Publications and source records attributed to S Matsuda.

At least 361 records · Page 20Linked to original sources
PubMed1994

Synergistic activation by Ras and 14-3-3 protein of a mitogen-activated protein kinase kinase kinase named Ras-dependent extracellular signal-regulated kinase kinase stimulator.

We have identified, in Xenopus oocyte cytosol, a protein kinase named REKS (Ras-dependent extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase kinase (MEK) stimulator), which phosphorylates and activates recombinant ERK2 through recombinant MEK in a recombinant GTP gamma S (guanosine 5'-(3-O-thio)triphosphate)-Ras-dependent manner. We show here that this REKS activity is synergistically enhanced by a combination of mammalian recombinant GTP gamma S-KiRas and 14-3-3 protein purified from rat brain. 14-3-3 protein is known to activate tyrosine and tryptophan hydroxylases, to modulate the protein kinase C activity, to stimulate secretion, and to show phospholipase A2 activity per se. 14-3-3 protein did not affect the MEK activity. 14-3-3 protein neither interacted with Ki-Ras nor affected the neurofibromin activity to stimulate the GTPase activity of Ki-Ras under the conditions where the recombinant N-terminal fragment of c-Raf-1 inhibited it. These results suggest that 14-3-3 protein has an additional function in the regulation of the Ras-MEK-ERK cascade pathway through the activation of REKS.

14-3-3 Proteins↗
PubMed1994

Basic fibroblast growth factor-like immunoreactivity in the rat basilar artery with reference to co-localization with NADPH-diaphorase in the trigeminal ganglion.

The location of basic fibroblast growth factor (bFGF)-like immunoreactivity and nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase (neuronal nitric oxide synthase) activity in the rat basilar artery and in the trigeminal, sphenopalatine and superior cervical ganglia was investigated. bFGF immunoreactivity was seen mainly in adventitial nerve fibers of the rat basilar artery, but not in the endothelium. Electron microscopy of the tunica media showed a number of immunoreactive nerve endings in the vicinity of local smooth muscle cells. Among the cranial ganglia that innervate the basilar artery, only the trigeminal ganglion had bFGF-immunoreactivity neurons. Nerve cells and fibers with NADPH-diaphorase activity were detected in the basilar artery and in the sphenopalatine and trigeminal ganglia, and the co-localization of bFGF and NADPH-diaphorase was noted only in the trigeminal ganglion. Furthermore, Fluro-gold tracing in combination with bFGF immunohistochemistry demonstrated that bFGF-containing nerve fibers in the wall of the basilar artery arise from the trigeminal ganglion. These findings provide a morphological basis for the nitric oxide-mediated dilatation of cerebral arteries by bFGF.

Animals↗
PubMed1994

Solution structure of the epidermal growth factor-like domain of heregulin-alpha, a ligand for p180erbB-4.

p185erbB-2 and p180erbB-4 are epidermal growth factor (EGF) receptor-like tyrosine kinases, whose co-expression is observed in many breast carcinomas. Heregulins (HRGs), which contain an immunoglobulin unit and an EGF-like domain, bind to p180erbB-4 and activate p180erbB-4 and p185erbB-2 through transphosphorylation or receptor heterodimerization. The EGF-like domain is sufficient for the activation. Despite the sequence similarity, no cross activity is seen between the p180erbB-4 ligands (HRGs) and the p170erbB-1 ligands [EGF and transforming growth factor (TGF)-alpha]. To investigate the structural basis of receptor specificity, we have determined the solution structure of the EGF-like domain of HRG-alpha by two-dimensional 1H nuclear magnetic resonance spectroscopy and simulated annealing calculations. Though its main-chain fold is similar to those of EGF and TGF-alpha, distinctive structural features are observed on the molecular surface including an ionic cluster and hydrophobic patches, which afford HRG-alpha the specific affinity for p180erbB-4. The structure should provide a basis for the structure-activity relationship of HRGs and for the design of drugs which prevent progression of breast cancer.

Amino Acid Sequence↗
PubMed1994

Feedback regulation of mitogen-activated protein kinase kinase kinase activity of c-Raf-1 by insulin and phorbol ester stimulation.

Recently, it has been reported that Raf-1 kinase (Raf-1) has mitogen-activated protein kinase kinase kinase (MAPKKK) activity in various cells, although Raf-1 and MAP kinase kinase (MAPKK) can be phosphorylated by MAP kinase (MAPK) in vitro. Here we show that the maximal hyperphosphorylation of Raf-1 and MAPKK (10 min) was substantially achieved after the maximal activation of MAPKKK of Raf-1, MAPKK (2-5 min), and MAPK in Chinese hamster ovary cells overexpressing human insulin receptor (CHO-HIR cells) treated with insulin or 12-O-tetradecanoylphorbol-13-acetate (TPA). Moreover, we show that overexpression of MAPK in CHO-HIR cells resulted in enhanced hyperphosphorylation of Raf-1, MAPKK, and mammalian homolog of son of sevenless (mSos) after insulin or TPA stimulation as compared with parental cells. Furthermore, the maximal hyperphosphorylation of Raf-1 appears to be accompanied by a significant decrease in MAPKKK activity. These results suggest that 1) signals initiated by insulin and TPA converge on Raf-1 and activate its MAPKKK activity and 2) Raf-1, MAPKK, and mSos not only lie upstream of MAPK but also are phosphorylated by MAPK, directly or indirectly, and at least Raf-1 kinase activity might be down-regulated by this feedback mechanism.

Amino Acid Sequence↗
PubMed1994

A meiotic DNA polymerase from a mushroom, Agaricus bisporus.

A meiotic DNA polymerase [DNA nucleotidyltransferase (DNA-directed), EC 2.7.7.7], which likely has a role in meiotic DNA repair, was isolated from a mushroom, Agaricus bisporus. The purified fraction displays three bands in SDS/PAGE, at molecular masses of 72 kDa, 65 kDa and 36 kDa. Optimal activity is at pH 7.0-8.0 in the presence of 5 mM Mg2+ and 50 mM KCl and at 28-30 degrees C, which is the temperature for meiosis. This enzyme is resistant to N-ethylmaleimide and sensitive to 2',3'-dideoxythymidine 5'-triphosphate, suggesting that it is a beta-like DNA polymerase. These characteristics are similar to those of Coprinus DNA polymerase beta [Sakaguchi and Lu (1982) Mol. Cell. Biol. 2, 752-757]. In Western-blot analysis, the antiserum against the Coprinus polymerase reacts only with the 65 kDa band, which coincides with the molecular mass of the Coprinus polymerase. Western-blot analysis also showed that the antiserum could react with crude extracts not only from the Agaricales family, to which Agaricus and Coprinus belong, but also from different mushroom families and Saccharomyces. The Agaricus polymerase activity can be found only in the meiotic-cell-rich fraction, but the enzyme is also present in the somatic cells in an inactive state.

Agaricus↗
PubMed1994

Arachidonate 12-lipoxygenase of rat pineal glands: catalytic properties and primary structure deduced from its cDNA.

When a crude extract of rat pineal glands (the 1000 x g supernatant of a homogenate) was incubated with arachidonic acid, 12-hydroxy-5,8,10,14-eicosatetraenoic acid was found as a major product. The 12-lipoxygenase of rat pineal gland also reacted with linoleic and alpha-linolenic acids at 35% and 101% the rate of arachidonate 12-oxygenation, respectively. Upon Western blot analysis using polyclonal antibody against porcine leukocyte 12-lipoxygenase, the cytosol fraction of rat pineal gland showed a positive band with a molecular weight of approx. 74 kDa. A full-length cDNA for this enzyme was cloned from a cDNA library of rat pineal gland and the identity of the 12-lipoxygenase cDNA was confirmed by its expression in E. coli. The amino acid sequence of the enzyme was deduced from the nucleotide sequence of the cDNA, encoding 663 amino acids with a calculated molecular weight of 75,305. The enzyme showed 72% identity of amino acid sequence with porcine leukocyte 12-lipoxygenase and 73% with bovine tracheal 12-lipoxygenase, but only 59% with human platelet 12-lipoxygenase. Taken together, the high reactivity with C-18 fatty acids, the immunoreactivity and the amino acid homology data indicate that the rat pineal 12-lipoxygenase is more closely related to leukocyte 12-lipoxygenase than to platelet 12-lipoxygenase. Upon RNA blot analysis, by far the highest content of 12-lipoxygenase mRNA was observed in the pineal gland and negligible amounts of mRNA were detected in other parts of the brain. The predominant presence of 12-lipoxygenase mRNA in pineal gland was confirmed by in situ hybridization of rat brain. Significant amounts of 12-lipoxygenase mRNA were also detected in rat spleen, aorta, lung and leukocytes.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1994

[Main household occupation and mean birth weight in Japan 1984].

By using the 1984 vital statistics released on magnet tapes by the Japanese government, we observed in the present study how the mean birth weight (MBW) varies from one group of mothers who fall under the same category of "main household job" to another. In so doing, we compared the MBWs among different job categories in terms of mother's age, baby's sex, and parity. The obtained results are summarized as follows: 1) The MBW of primiparae and male babies was found to be significantly different among the job categories in the age range of 20-39. In the group of multiparae and male babies, however, all the age ranges older that twenty showed significant differences in the MBW among the job categories. In the group of female babies, the significant difference was found in the age range of 20-39 and all the ranges older than twenty for primiparae and multiparae, respectively. 2) The above results were considered to be caused mainly by the low MBW in the category of "other" for primiparae, and by the high MBW in "part-time farming" and the low MBW in "other" for multiparae.

Adolescent↗
PubMed1994

Signaling pathways mediated by the mitogen-activated protein (MAP) kinase kinase/MAP kinase cascade.

Mitogen-activated protein (MAP) kinase and its direct activator, MAP kinase kinase (MAPKK), comprise the MAPKK/MAP kinase cascade, which may play a pivotal role in a variety of intracellular signal transduction pathways from yeast to human. Vertebrate MAPKK, a dual-specificity kinase, is activated by serine phosphorylation catalyzed by upstream serine/threonine kinases, MAPKK kinases (MAPKK-Ks). MAPKK is, on the other hand, threonine phosphorylated by MAP kinase, although a physiological role of this MAP kinase-mediated phosphorylation of MAPKK is unknown. Biochemical fractionation of extracts from Xenopus mature oocytes revealed two major and one minor peaks for the MAPKK-K activity. One of the major peaks contained a proto-oncogene product c-Mos, while the other peaks did not. These observations, together with a recent finding that several MAPKK-Ks such as Raf-1 and MEKK may function within a cell, suggest a diversity of MAPKK-Ks. A variety of extracellular signals converge at the MAPKK/MAP kinase cascade through different MAPKK-Ks and elicit a wide spectrum of cellular responses. Therefore, mechanisms that control activation of the MAP kinase cascade temporally and spatially may be important for specification of cellular responses.

Animals↗
PubMed1994

Calcium regulating activity of 26,27-dimethyl analog of 24R,25-dihydroxyvitamin D3.

To determine the possibility that methyl substitution in 26- and 27-positions of 24R,25-dihydroxyvitamin D3 [24,25(OH)2D3] alters activities of the original compound, the effects of 24,25(OH)2D3 on calcium (Ca) regulating activity were compared with those of its methyl analog [24,25(OH)2(CH3)2D3] in addition to 1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3]. 24,25(OH)2D3 at 10(-6) M and 24,25(OH)2(CH3)2D3 at 10(-7) M and above significantly stimulated both bone resorption in neonatal mouse calvaria cultures and formation of osteoclast-like multinucleated cells (MNC) in mouse bone marrow cultures. A stimulative effect of 1,25(OH)2D3 on bone resorption and MNC formation was recognized in very low concentrations (10(-11) M and above). Although a potency of 24,25(OH)2(CH3)2D3 in stimulating bone calcium (Ca) mobilization and intestinal Ca transport was higher than that of 24,25(OH)2D3, the potencies of both compounds were similar to that of 1,25(OH)2D3 unlike in vitro experiments. As 1,24R,25-trihydroxy-26,27-dimethylvitamin D3 showed almost the same effect as 24,25(OH)2(CH3)2D3, the dihydroxy form is suggested to be hydroxylated at 1 alpha position and converted to trihydroxy form in vitamin D-deficient rats. From these results, methyl substitution in 26- and 27-position of 24,25(OH)2D3 was found to elevate Ca regulating activity of the original compound. In addition, it is suggested that the basis for a similarity in potency between 1,25(OH)2D3 and 24,25(OH)2D3 or its dimethyl analog in vitamin D-deficient rats is likely the result of 1 alpha-hydroxylation.

24,25-Dihydroxyvitamin D 3↗
PubMed1994

Development of Purkinje cell bodies and processes with basic fibroblast growth factor-like immunoreactivity in the rat cerebellum.

The development of basic fibroblast growth factor-like immunoreactivity was investigated in the nuclei, cell bodies and processes of Purkinje cells with attention to basic fibroblast growth factor-containing neuronal input to the deep cerebellar nuclei. Immunoblot analysis with the use of the antisera against basic fibroblast growth factor revealed that crude homogenate of the developing rat cerebellum exhibits a main band with the same molecular weight (18,000 mol. wt) as basic fibroblast growth factor in all the postnasal stages examined. Cerebellar cells were not labeled with the antisera during embryonic life. Under light microscopy, basic fibroblast growth factor-like immunoreactivity was detected initially in cortical cells located close to deep cerebellar fissures of the newborn rat but not in superficial cortical regions. It was difficult to determine whether or not they are Purkinje cells at the fusiform stage. On postnatal day 7, immunoreactive Purkinje cells were identified throughout the cerebellar cortex, and they expressed basic fibroblast growth factor-like immunoreactivity mainly in the apical cytoplasm and proximal dendrites. From postnatal day 14 to postnatal day 28, basic fibroblast growth factor-like immunoreactivity was noted not only throughout the cytoplasm of Purkinje cells but also in the nuclei of the immunopositive cells. Our statistical analysis showed that Purkinje cells with nuclear immunoreaction peaked on postnatal day 21. At these stages, nerve fibers immunoreactive for basic fibroblast growth factor were numerous in the cerebellar medulla and deep cerebellar nuclei. After postnatal day 42, Purkinje cells with intense immunoreactivity in the nuclei showed a marked decrease in number, and immunoreactive structures were distributed in the cerebellum in a fashion similar to that in adult rats. Electron microscopy demonstrated that immunoreactivity was located mainly in the apical cytoplasm of Purkinje cells on postnatal day 7 and throughout the cytoplasm and in the nuclear euchromatin from postnatal day 14 to postnatal day 28, as was expected from light-microscopic observations. Immunoreactivity, even though distributed diffusely in the cytoplasm, was absent from the lumen of endoplasmic reticulum and mitochondria. A small population of Purkinje cell axon terminals forming synapses with the soma and dendrites of deep cerebellar nucleus neurons began to express basic fibroblast growth factor on postnatal day 21. This is much later than the starting age for synaptogenesis between Purkinje cells and deep cerebellar nucleus neurons. The age-dependent changes in the localization of basic fibroblast growth factor within Purkinje cell nucleus, soma and processes suggest a complex transport system of this factor within Purkinje cells during postnatal development.

Aging↗
PubMed1994

Magnetic resonance imaging assessment of the temporomandibular joint in disk displacement.

Twenty-four patients (48 joints) presenting signs and symptoms of internal derangement of the temporomandibular joint (TMJ) were studied, combinations of coronal and sagittal magnetic resonance imaging (MRI) being used for assessment of the TMJ disk. In the coronal MRI, lateral or medial disk displacement was confirmed in 10/48 joints (20.8%). Disk displacement in a lateral direction was confirmed in six joints, and in a medial direction in four joints, while, in the sagittal images, anterior displacement of the disk without reduction (ADWR) was observed in 20/48 joints (17/24 cases), among which bilateral ADWR were found in three cases. Rotational disk displacements were observed in eight joints, and of these cases six were anterior and lateral disk displacements, while the remaining two were anterior and medial disk displacements. The disks tended to be displaced in a lateral direction in cases of rotational disk displacement.

Adolescent↗
PubMed1994

Origin of ischemia-induced glutamate efflux in the CA1 field of the gerbil hippocampus: an in vivo brain microdialysis study.

In vivo brain microdialysis experiments were performed in the gerbil to evaluate the origin of accumulation of extracellular glutamate under transient ischemia. Microdialysis probes were positioned in the CA1 field of the hippocampus in which proliferation of astrocytes, death of CA1 pyramidal neurons, and damage of presynaptic terminals had been induced by 5-min ischemia 10-14 days before the microdialysis experiment; in the white matter of the cerebral cortex, which contained few neurons, few presynaptic terminals, and many astrocytes; or in the histologically normal CA1 field of the hippocampus, and then 5- or 20-min ischemia was induced. When 5-min ischemia was induced, no significant increase in glutamate content was observed in the CA1 field that showed proliferation of astrocytes, death of CA1 pyramidal neurons, and damage of presynaptic terminals and in the white matter of the cerebral cortex, whereas a significant increase in glutamate (15-fold) was observed in the histologically normal CA1 field. When 20-min ischemia was induced, no significant increase in glutamate content was observed in the CA1 field that showed proliferation of astrocytes, death of CA1 pyramidal neurons, and damage of presynaptic terminals and in the white matter during the first 10 min after the onset of 20-min ischemia, but remarkable ischemia-induced increases in glutamate were observed during the last 10 min of 20-min ischemia in both areas. An excessive increase in glutamate (100-fold) was observed during 20-min ischemia in the normal CA1 field of the hippocampus. When a probe was positioned in the CA1 field of the hippocampus in which presynaptic terminals of Schaffer collaterals and commissural fibers had been eliminated by bilateral kainate injections into the lateral ventricles 4-7 days before the microdialysis experiment and then 5-min ischemia was induced, a significant increase in glutamate was observed during the last half of 5-min ischemia. These results suggest that the efflux of glutamate from astrocytes does not contribute to the large ischemia-induced glutamate accumulation in the CA1 field of the hippocampus during 5-min ischemia but contributes to the ischemia-induced increase in glutamate level during ischemia with a longer duration and that ischemia-induced efflux of glutamate in the CA1 field during 5-min ischemia originates mainly from neuronal elements: presynaptic terminals and post-synaptic neurons.

Animals↗
PubMed1994

Synthesis of 12(R)- and 12(S)-hydroxyeicosatetraenoic acid by porcine ocular tissues.

Microsomal fractions from porcine ocular tissues synthesized 12(S)-5,8,10,14-hydroxyeicosatetraenoic acid [12(S)-HETE] from arachidonic acid by a membrane-bound lipoxygenase and 12(R)-HETE by the cytochrome P450-dependent monooxygenase system. Both activities were the highest in corneal microsomes. The 12(R)-HETE synthesizing activity of corneal microsomes was dependent on NADPH and inhibited by 0.1 mM SKF-525A, an inhibitor of P450 enzymes. The activity to form 12(R)-enantiomer was significantly enhanced by treatment of corneal epithelium with 3-methylcholanthrene or clofibrate. The induced activity was suppressed by cycloheximide, indicating that the induction of enzyme activities involved a translational process. The effect of these inducers on 12(R)-HETE synthesizing activity appeared to be additive. The activity to form 12(S)-enantiomer was markedly stimulated by 3 mM CaCl2. The 12-lipoxygenase of corneal microsomes was capable of oxygenating linoleic acid in addition to arachidonic acid, a characteristic of 12-lipoxygenases of the leukocyte type. 12(R)-HETE at 10(-6) M inhibited almost completely the Na,K-ATPase of corneal epithelium but had little or no effect on ciliary epithelial enzymic activity. 12(S)-HETE at 10(-6) M also inhibited corneal enzymic activity but to a lesser extent, and had no significant effect on ciliary epithelial Na,K-ATPase activity.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1994

Geographical differences and time trends in the seasonality of birth in Japan.

Seasonal variations of births in six different prefectures in Japan are analysed using Vital Statistics from 1974 to 1983. First births show a bimodal pattern with two peaks, one in winter (December-February) and the other in summer to early autumn (August-September). The seasonality of first births is statistically significantly correlated with the seasonality of marriages with 9 + 12*n (n = 0, 1, 2, 3) lag months. For subsequent births, the seasonal pattern is unimodal and there is also a geographical trend in seasonality of these births with a late spring peak in the northernmost prefecture of Japan giving way to an early autumn peak in the southernmost prefecture. These findings suggest that seasonal variations in marriage play some role in the seasonality of first births, while other features such as environmental factors could be associated with the seasonal variations of subsequent births. Changes in the seasonality of both births and marriages over time suggest that the modernization of Japanese society after the second World War could be responsible for the drastic changes in the pattern and degree of seasonality of births.

Analysis of Variance↗
PubMed1994

Characterization of p59fyn-mediated signal transduction on T cell activation.

Protein tyrosine kinase p59fyn is associated with the TCR-CD3 complex and is suggested to play a role in T cell activation. To determine the molecular mechanism of p59fyn-mediated signal transduction in T cell activation, we established murine T cell hybridoma lines that expressed an elevated amount of wild-type or mutant fyns. Clones that expressed high levels of normal p59fyn and active p59fyn, encoded by wild-type and f-14 mutant fyn respectively, showed enhanced IL-2 production upon stimulation by anti-CD3 antibodies or natural antigen. On the other hand, clones that expressed kinase negative p59fyn and p59fyn with an SH2 (Src-homology 2) deletion encoded by t-1 mutant fyn showed little induction of IL-2 production upon stimulation. These data suggest that p59fyn is important in T cell signaling and that the SH2 sequence plays a critical role in the reaction. Induction of tyrosine phosphorylation of multiple proteins upon antigenic stimulation was augmented similarly in the cells that respectively expressed wild-type and f-14 mutant fyns at elevated levels. The proteins that became highly tyrosine-phosphorylated included phospholipase C (PLC-gamma 1), p95vav, ZAP-70, the MAP kinase, CD3 zeta and unidentified proteins of 120, 100 and 80 kDa. Tyrosine phosphorylation of the 120, 95 and 68 kDa proteins associated with PLC-gamma 1 was also observed in these cells upon stimulation. In contrast, only the 100 kDa protein and the MAP kinase were increasingly tyrosine phosphorylated in the antigen-stimulated cells expressing t-1 fyn. These data suggest that PLC-gamma 1, PLC-gamma 1 associated molecules, p95vav, the 80 kDa protein, ZAP-70 and the CD3 zeta chain may be substrates of p59fyn or of other tyrosine kinases regulated by p59fyn and be important in T cell signaling.

Animals↗
PubMed1994

Pemphigus vulgaris associated with autoimmune hemolytic anemia and elevated TNF alpha.

A 76-year-old female was admitted with many bullae and erythema on her trunk and extremities. A biopsy specimen showed significant intercellular edema in the lower epidermis and eosinophilic infiltration into the dermis and the epidermis. Immunofluorescent staining revealed the deposition of IgG in the intercellular area of her prickle cells. From these histologic findings and the typical clinical features, we diagnosed her as having pemphigus vulgaris. Examination of her blood revealed that she also suffered from autoimmune hemolytic anemia. Despite intensive treatment with prednisolone, she finally died. This case is of interest because of its rarity and the TNF alpha detected significantly in the blister fluid of this patient.

Aged↗
PubMed1994

Long-Evans A and C rat strains susceptible to clastogenic effects of chemicals in the bone marrow cells.

The clastogenic responses to direct- and indirect-acting carcinogens in bone marrow cells of LEA, LEC, Wistar and SD rats were compared. The frequency of chromosome aberrations (CA) induced by n-butyl-N-nitrosourea or methylmethanesulfonate (MMS), which does not need metabolic activation, was significantly higher in both LEA and LEC rats than in Wistar or SD rats. When bone marrow cells of each rat strain were exposed to MMS in vitro, they also showed the same tendency in CA frequency. Therefore, the high sensitivity of both LEA and LEC rats to the clastogenic effects of direct-acting carcinogens seems to result from the sensitivity of the bone marrow cells themselves. On the other hand, the CA frequency induced by 7,12-dimethylbenz[a]anthracene (DMBA) or aflatoxin B1 (AFB1), which requires metabolic activation, was lower in LEC rats than in the other 3 strains. The CA frequency induced by DMBA or AFB1 in LEC rats fed Cu-free diet since birth (Cu-free LEC rats) was higher than that in LEC rats given normal diet and lower than that in LEA rats, although the difference was statistically significant only between Cu-free LEC rats and LEC rats treated with DMBA. The copper concentrations in the livers of LEA, Cu-free LEC and LEC male rats aged 4 weeks were 5.0 +/- 0.4, 33 +/- 7.7 and 106 +/- 3.4 micrograms/g wet weight, respectively. These results suggest that the lower sensitivity of LEC rats to the clastogenic effects of indirect-acting carcinogens may be due to the effect of the large amount of copper accumulated in LEC rat liver.

9,10-Dimethyl-1,2-benzanthracene↗