Biomedical subjects

D Roy

Publications and source records attributed to D Roy.

At least 37 records · Page 2Linked to original sources

PubMed1997

Endovascular treatment of ophthalmic segment aneurysms with Guglielmi detachable coils.

PURPOSE: To evaluate the safety and efficacy of endovascular treatment of ophthalmic segment aneurysms with Guglielmi detachable coils (GDCs), as well as the primary indications for such treatment. METHODS: We conducted a prospective study of 26 patients with 28 aneurysms of the ophthalmic segment in whom treatment with GDCs was attempted. Anatomic results were measured by statistical analysis of variance for such factors as age, sex, presence of subarachnoid hemorrhage, anatomic type (ophthalmic or superior hypophyseal), size of aneurysmal sac, and width of aneurysmal neck. Clinical evaluation and control angiography were performed at 6 and 18 months. RESULTS: Overall, complete occlusion was obtained in 14 aneurysms (50%) and small residual necks were left in 11 aneurysms (39%). Three treatment attempts failed (11%). Complete occlusion was obtained in 76% of small-necked aneurysms as opposed to 9% of aneurysms with a large neck. The best predictor of anatomic result was the size of the aneurysmal neck. Complete occlusion was obtained in 85% of superior hypophyseal aneurysms of the paraclinoid variant. One permanent complication was related to treatment. CONCLUSION: Endovascular treatment with GDCs appears to be a safe and efficient alternative approach for ophthalmic segment aneurysms, especially for paraclinoid variants of superior hypophyseal aneurysms, which tend to have a small neck.

Adult↗

PubMed1996

Control of heart rate during transition from intravenous to oral diltiazem in atrial fibrillation or flutter.

We tested whether patients presenting with atrial fibrillation (AF) or flutter (AFl) with a rapid ventricular response could maintain control of heart rate while transferring from a bolus and continuous infusion of intravenous diltiazem to oral diltiazem. Forty patients with AF or AFI and sustained ventricular rate > or = 120 beats/min received intravenous diltiazem "bolus" (20 to 25 mg for 2 minutes) and "infusion" (5 to 15 mg/hour for 6 to 20 hours). Oral long-acting diltiazem (diltiazem CD 180, 300, or 360 mg/24 hours) was administered in patients in whom stable heart rate control was attained during constant infusion. Intravenous diltiazem infusion was discontinued 4 hours after the first oral dose, and patients were monitored during 48 subsequent hours of "transition" to oral therapy. Response to diltiazem was defined as heart rate <100 beats/min, > or = 20% decrease in heart rate from baseline, or conversion to sinus rhythm. Other rate control or antiarrhythmic medications were not allowed during the study period. Thirty-seven of 40 patients maintained heart rate control during the bolus, and 35 of the remaining 37 maintained control during the infusion of intravenous diltiazem. Of the 35 patients achieving heart rate control with intravenous diltiazem who entered the transition to oral therapy, 27 maintained heart rate control (response rate of 77%/, 95% confidence interval 63% to 91%). The median infusion rate of intravenous diltiazem was 10 mg/hour, and the median dose of oral diltiazem CD was 300 mg/day. Oral long-acting diltiazem was 77% effective in controlling ventricular response over 48 hours in patients with AF or AFl in whom ventricular response was initially controlled with intravenous diltiazem.

Administration, Oral↗

PubMed1996

Apoptosis of cardiac myocytes during cardiac allograft rejection. Relation to induction of nitric oxide synthase.

BACKGROUND: Apoptosis is a distinct form of programmed cell death characterized by activation of endonucleases that cleave nuclear DNA, condensation and fragmentation of nuclear chromatin, blebbing of intact membranes, and cell shrinkage and fragmentation. The mechanisms responsible are unclear, but nitric oxide (NO) generated by inducible NO synthase (iNOS) has been demonstrated to induce apoptosis in macrophages in vitro. This study investigated whether apoptosis occurs during cardiac allograft rejection and examined the relationship of apoptosis to iNOS expression. METHODS AND RESULTS: Heterotopic abdominal transplantation from Lewis to Wistar-Furth rats was used as a model of cardiac allograft rejection; Lewis-to-Lewis grafts served as controls. Apoptosis was identified by DNA ladders after electrophoresis on agarose gels and by in situ labeling of DNA fragments; cell types were determined by immunohistochemistry. The number of apoptotic cardiac myocytes increased sharply from day 3 (0.31/mm2 ventricular tissue) to day 5 (1.27/mm2) after transplantation. At day 5, allografts showed a significant increase (P < .01) in apoptotic cardiac myocytes, macrophages, and endothelial cells compared with syngeneic grafts. The expression of iNOS mRNA, protein, and enzyme activity paralleled in time and extent the apoptosis of cardiac myocytes. iNOS immunostaining of infiltrating macrophages and cardiac muscle fibers increased significantly in the allografts at days 3 to 5 and was accompanied by immunostaining of both cell types for nitrotyrosine, which is indicative of peroxynitrite formation. CONCLUSIONS: Apoptosis of myocardial cells occurs during cardiac allograft rejection. Apoptosis during rejection parallels the expression of iNOS, which suggests that apoptosis may be triggered by NO and peroxynitrite.

Animals↗

PubMed1996

Inhibition of stilbene estrogen-induced cell proliferation of renal epithelial cells through the modulation of insulin-like growth factor-I receptor expression.

In the present study, we have investigated the effects of stilbene estrogen, diethylstilbestrol (DES), on the proliferative activity and expression of insulin-like growth factor-I (IGF-I) receptor in Syrian hamster renal epithelial cells. DES exposure to renal epithelial cells caused both dose- and time-dependent increases in proliferative activity. We also tested the effects of antiestrogen ICI 182780 and insulin-like growth factor-I receptor (IGF-IR) antibody on cell proliferation. Cotreatment of cells with ICI 182780 (250 nM) and DES resulted in a 50% decrease in cell growth compared to DES alone. Treatment of cells with an anti-IGF-IR antibody (alpha IR3, 1 microgram/ml) also significantly reversed the growth-stimulatory effects of DES. A nuclear binding assay revealed that an enhanced level (approximately 2-fold) of [125I]IGF-I binding to nuclear protein occurred in DES treated renal epithelial cell nuclei compared to controls. IGF-I receptor gene expression analyzed by Northern blotting revealed that DES treatment increased the level of IGF-IR mRNA by 2-fold compared to controls. We also tested the effect of ICI compound on the induction of IGF-I receptor gene. The cotreatment of ICI 182780 strongly inhibited DES-induced IGF-I receptor gene expression (50-60% inhibition). Stimulation of the proliferative activity of renal epithelial cells by stilbene estrogen, its prevention by IGF-I receptor antibody, and inhibition of DES-induced proliferative activity and the expression of IGF-I receptors by ICI 182780 suggest the possibility that the stimulatory effect of DES on the proliferative activity of renal epithelial cells may be mediated through the up-regulation of IGF-I receptors.

Animals↗

PubMed1996

Exercise induces the translocation of GLUT4 to transverse tubules from an intracellular pool in rat skeletal muscle.

Exercise stimulates glucose transport in skeletal muscle by increasing the number of GLUT4 glucose transporters at the cell surface. The effect of exercise on GLUT4 content in transverse tubules, which are deep extensions of the plasma membrane involved in myofiber contraction, has never been studied. In the present study, we have investigated whether acute exercise induces translocation of GLUT4 to the transverse tubules. Plasma membranes and transverse tubules were isolated from control and exercised rats by a newly developed membrane fractionation procedure. As expected, acute exercise increased GLUT4 content in plasma membranes (95%; p < 0.01). Importantly, exercise also significantly increased GLUT4 content in a transverse tubule-enriched fraction (60%; p < 0.05). Furthermore, acute exercise was found to decrease GLUT4 content in an intracellular membrane fraction (-40%; p < 0.001). In conclusion, this study demonstrates that GLUT4 is translocated not only to the plasma membranes but also to the transverse tubules in acutely exercised muscles. The results also indicate that GLUT4 is recruited from a novel intracellular membrane fraction.

5'-Nucleotidase↗

PubMed1996

Factors determining compliance with screening mammography.

OBJECTIVE: To determine factors affecting compliance with screening mammography prescribed by family physicians. DESIGN: Secondary analysis of a nonrandomized trial. SETTING: University-affiliated family medicine clinic in Montreal. PATIENTS: Women aged 50 to 69 years who were given a written prescription for a screening mammography during their visit at the clinic between Oct. 12, 1991, and May 31, 1992, and who had not undergone mammography in the preceding 2 years and had never been treated for breast cancer. Information on the potential factors was obtained through a telephone questionnaire 2 months after the visit. OUTCOME MEASURES: Indicator of compliance presence of result of screening mammography in patient chart, potential factors influencing compliance: age, level of education, marital status, socioeconomic level, smoking status, perceived health status, perceived psychological well-being, risk factors for breast cancer, use of health services including frequency of Papanicolaou test, Health Belief Model variables. RESULTS: Of the 171 eligible women, 113 (66.1%) underwent the prescribed mammography within 2 months after the visit to the clinic, and 149 (87.1%) responded to the questionnaire. The patients' socioeconomic characteristics, perceived health status, health utilization indices and risk factors for breast cancer were not found to be predictors of compliance. The strongest predictor of compliance was the number of previous mammograms. Women who had undergone mammography previously were less likely to be noncompliant than those who had not (odds ratio [OR] 0.11, 95% confidence interval [CI] 0.02 to 0.51; p = 0.005). Women who did not comply were less likely than those who did to believe that a prescription from their physician would convince them to undergo mammography (OR 0.21, 95% CI 0.007 to 0.60; p = 0.004). Other factors associated with noncompliance were the expression of fear of mammography (OR 2.09, 95% CI 1.08 to 4.02; p = 0.03) and the lack of time to take the test (OR 3.07, 95% CI 1.21 to 7.80 p = 0.02). Being a smoker was negatively associated with compliance (OR 0.43; 95% CI 0.22 to 0.86; p = 0.02). The stepwise logistic regression model accounted for 87.5% of the outcome (chi2 for goodness of fit = 164.4; p = 0.0001). CONCLUSION: Family physicians who prescribe screening mammography, even to women who consult for other reasons, are likely to overcome some of the barriers observed in association with population screening rates. However, physician-oriented approaches are not likely to reach the 30% to 40% of reluctant women who appear to hold negative views toward physicians' recommendations. Further study is necessary to determine how better to reach these women.

Aged↗

PubMed1996

Up-regulation of nuclear IGF-I receptor by short term exposure of stilbene estrogen, diethylstilbestrol.

In the present study we report the novel findings that IGF-I receptors are present in the nucleus based on the evidence from binding assay, detection of receptors by affinity labeling and Western blotting, and localization by immunofluorescence. The level of nuclear IGF-I receptors (nIGF-IRs) almost doubled in stilbene estrogen (diethylstilbestrol, DES) treated hamster kidneys compared to the controls. The binding constants Kd and Bmax of nIGF-IR of controls, 22.1 nM and 6.6 nmol/mg protein, respectively, were changed in response to DES treatment to 5.3 nM and 16.3 nmol/mg protein (P < 0.001), respectively. The enhanced level of IGF-IR in DES-treated nuclei was confirmed by both affinity labeling and Western blotting. These data suggest that IGFs may exert their biological effect through the IGF-I receptor present in the nucleus. Whether the up-regulation of nIGF-IR by exposure to a carcinogenic dose of DES may be a factor in the induction of renal cancer in Syrian hamsters, is not clear.

Animals↗

PubMed1996

Biochemical characterization of a mitomycin C-resistant human bladder cancer cell line.

This study describes characteristics of a mitomycin C (MMC)-resistant human bladder cancer cell line, J82/MMC-2, which was established by repeated in vitro exposures of a 6-fold MMC-resistant variant (J82/MMC) to 18 nM MMC. A 9.6-fold higher concentration of MMC was required to kill 50% of the J82/MMC-2 sub-line compared with parental cells (J82/WT). NADPH cytochrome P450 reductase and DT-diaphorase activities were significantly lower in J82/MMC-2 cells compared with J82/WT, suggesting that reduced sensitivity of J82/MMC-2 cells to MMC resulted from impaired drug activation. Consistent with this hypothesis, the formation of MMC-alkylating metabolites was significantly lower in J82/MMC-2 cells compared with J82/WT. Furthermore, DT-diaphorase activity in J82/MMC-2 cells was significantly lower compared with the 6-fold MMC-resistant variant. Glutathione (GSH) levels were comparable in all 3 cell lines. Although GSH transferase (GST) activity was significantly higher in the J82/MMC-2 cells compared with J82/WT, this enzyme activity did not differ between 6- and 9.6-fold MMC-resistant variants. Whereas DNA polymerase alpha mRNA expression was comparable in these cell lines, levels of DNA ligase I mRNA were slightly lower in both MMC-resistant variants relative to J82/WT. However, the DNA polymerase beta mRNA level was markedly higher in the J82/MMC-2 cell line compared with either J82/WT or J82/MMC. Thus, emergence of a higher level of resistance to MMC in J82/MMC-2 cells compared with J82/MMC may be attributed to (i) impaired drug activation through further reduction in DT-diaphorase activity and (ii) enhanced DNA repair through over-expression of DNA polymerase beta.

Antibiotics, Antineoplastic↗

PubMed1996

Zinc and iron as bioindicators of precancerous nature of oral submucous fibrosis.

Oral Submucous Fibrosis (OSF) is a precancerous condition of oral cavity and oropharynx. Its etiopathogenesis is still obscure. Epithelial dysplasia is considered an important indicator of it. In the present study, the authors try to ascertain bioinorganic parameters as alternate indicators of malignant potential of OSF along with other clinicopathological attributes. They also try to identify causative factors. Thirty-six OSF patients, showing different degrees of epithelial dysplasia, and 12 normal individuals are studied with special reference to trace metal contents (Zn and Fe) in oral tissues. Statistical analyses of data indicate that trace metal contents can be regarded as an alternate indicator of the precancerous nature of OSF. Some clinicopathological attributes that are easier and cheaper to measure may also indicate OSF.

Adult↗

PubMed1996

Differentiation of bifidobacteria by use of pulsed-field gel electrophoresis and polymerase chain reaction.

Several different genomic fingerprints can be obtained from various commercially-important species of Bifidobacterium using pulsed-field gel electrophoresis (PFGE) following digestion of DNA with XbaI and SpeI. Four different genomic finger printings were discernible for reference strains of Bifidobacterium animalis, five for B. bifidum, three for B. breve, five for B. infantis and three for B. longum. Standard commercially-available industrial strains of B. animalis are identical to the reference strain ATCC 27536, previously isolated from chicken feces. There was more genomic heterogeneity among industrial strains of B. longum, in that only one gave profiles similar to the type strain of this species (ATCC 15707). The other 14 commercially-available strains of B. longum (mainly isolated from Japanese commercial preparations) were divided into four new molecular types based on their PFGE patterns. The PFGE method indicated that only five distinct strains of B. longum and one strain of B. animalis are used in commercial preparations. Additionally, the use of polymerase chain reaction amplification of portions of 16S rDNA provides a highly specific technique to discriminate between the species B. breve, B. infantis and B. longum.

Adult↗

PubMed1996

Insulin-induced translocation of Na+-K+-ATPase subunits to the plasma membrane is muscle fiber type specific.

We have previously shown that an acute insulin treatment induces redistribution of the alpha 2- and beta 1- isoforms of the Na+-K+-ATPase from intracellular membranes to plasma membranes detected on subcellular fractionation of mixed muscles and immunoblotting with isoform-specific antibodies (H. S. Hundal et al. J. Biol. Chem. 267: 5040-5043, 1992). In the present study we give both biochemical and morphological evidence that this insulin effect is operative in muscles composed mostly of oxidative (red) fibers but not in muscles composed mostly of glycolytic (white) fibers. The redistribution of the Na+-K+-ATPase alpha 2- and beta 1-isoforms after insulin injection was detected in membranes isolated from and muscles (soleus, red gastrocnemius, red rectus femoris, and red vastus lateralis) but not in membranes from white muscles (white gastrocnemius, tensor fasciae latae, white rectus femoris, and white vastus lateralis). After insulin injection, the potassium-dependent 3-O-methylfluorescein phosphatase activity of the enzyme was higher by 22% in the plasma membrane-enriched fraction and lower by 15% in the internal membrane fraction isolated from red but not from white muscles. Quantitative immunoelectron microscopy of ultrathin muscle cryosections showed that in vivo insulin stimulation augmented the density of Na+-K+-ATPase alpha 2- and beta 1- isoforms at the plasma membrane of soleus muscle by 80 and 124%, respectively, with no change in white gastrocnemius muscle. The effect of insulin to increase the content of Na+-K+-ATPase alpha 2- and beta 1-subunits in isolated plasma membranes was still observed when glycemia was prevented from dropping by using hyperinsulinemic-euglycemic clamps. We conclude that the insulin-induced redistribution of the alpha 2- and beta 1-isoforms of the Na+-K+-ATPase from an intracellular pool to the plasma membrane in restricted to oxidative fiber-type skeletal muscles. This may be related to the selective expression of beta 1-subunits in these fibers and implies that the beta 2-subunit, typical of glycolytic muscles, does not sustain translocation of alpha 2 beta 2-complexes.

Animals↗

PubMed1996

A new procedure for the isolation of plasma membranes, T tubules, and internal membranes from skeletal muscle.

A new subcellular fractionation procedure for the simultaneous isolation of plasma membranes and transverse (T) tubule membranes from a rat skeletal muscle was developed. This new technique allows the isolation and separation of plasma membranes and T tubules in distinct subcellular fractions, as revealed by the membrane distribution of enzymatic and immunologic markers of both cell surface compartments. The procedure also yields a novel membrane fraction that is devoid of markers of both surface domains but is markedly enriched with GLUT-4 glucose transporters, thus strongly suggesting that it represents an intracellular pool of GLUT-4. Using this new procedure, we found that acute in vivo insulin administration (30 min) increased GLUT-4 protein content in the plasma membrane and a T tubule fraction (by approximately 80%), whereas a smaller elevation (35%) was observed in another fraction enriched with T tubules. Insulin induced a concomitant reduction (approximately 40%) in GLUT-4 abundance in the intracellular fraction. These results further support the hypothesis that T tubules are involved in the regulation of glucose transport in skeletal muscle. This novel fractionation method will be useful in investigating the regulation of muscle GLUT-4 transporters in other physiological and disease states such as diabetes, where defective translocation of the transporter protein to either one or both cell surface domains is suspected to occur.

Animals↗

PubMed1996

Association of antithrombotic factor deficiencies and hypofibrinolysis with Legg-Perthes disease.

Thirty-three (75 per cent) of forty-four unselected children who had Legg-Perthes disease were found to have coagulation abnormalities. Twenty-three children had thrombophilia (a deficiency in antithrombotic factor C or S, with an increased tendency toward thrombosis); nineteen of the twenty-three children had protein-C deficiency and four had protein-S deficiency. Seven children had a high level (0.25 gram per liter or more) of lipoprotein(a), a thrombogenic, atherogenic lipoprotein associated with osteonecrosis in adults. Three children had hypofibrinolysis (a reduced ability to lyse clots). The mean age of the children when the Legg-Perthes disease was first diagnosed was 5.8 +/- 2.7 years, and the mean age at the time of the present study was 10.1 +/- 4.4 years. At least one of the first-degree relatives of eleven of the nineteen probands who had a low protein-C level had a low protein-C level as well; all of these low levels represented previously undiagnosed familial protein-C deficiency. The eleven probands who had familial protein-C deficiency were more likely to have early onset of Legg-Perthes disease (at or before the age of five years) than the eleven children who had normal levels of protein C, protein S, and lipoprotein(a) as well as normal fibrinolytic activity (chi-square = 6.6; p = 0.01). At least one first-degree relative of one of the four probands who had a low protein-S level had a low protein-S level and previously undiagnosed familial protein-S deficiency. At least one first-degree relative of six of the seven probands who had a high level of lipoprotein(a) had a familial high level of lipoprotein(a). Six of the seven children who had a high level of lipoprotein(a) also had a low level of stimulated tissue-plasminogen activator activity, the major initiator of fibrinolysis. At least one first-degree relative of one of the three probands who had normal levels of protein C, protein S, and lipoprotein(a) but low stimulated tissue-plasminogen activator activity also had low stimulated tissue-plasminogen activator activity (familial hypofibrinolysis). Legg-Perthes disease, thrombophlebitis, premature myocardial infarction, and stroke, which are ramifications of the familial thrombophilic-hypofibrinolytic disorders, were common in the first and second-degree relatives of the thirty-three children with Legg-Perthes disease who also had thrombophilic-hypofibrinolytic disorders.

Adolescent↗

PubMed1996

Direct intraoperative sclerotherapy of an aneurysmal bone cyst of the sphenoid.

A young boy presented with a symptomatic aneurysmal bone cyst of the left great wing of the sphenoid bone. Arterial embolization had failed to produce thrombosis, and the lesion could not be resected surgically. Direct intraoperative sclerotherapy resulted in immediate thrombosis of 80% of the volume of the vascular malformation with no progression of symptoms. Two years later, the symptoms had completely resolved, and CT scans showed total ossification of the lesion.

Arteriovenous Malformations↗

PubMed1996

[Acute torsion of an accessory spleen].

A case of acute torsion of an accessory spleen is reported. In a 15-year-old girl was admitted to hospital with acute abdominal pain. Ultrasonography showed a round, hypoechoic, solid mass. Computed tomography demonstrated a low-density mass with peripheral enhancement after intravenous contrast medium. These findings suggest the presence of a capsule. At laparotomy, the patient was found to have torsion and infarction of an accessory spleen. Sonographic and computed tomographic findings are discussed.

Acute Disease↗

PubMed1995

Perturbation of cell cycle kinetics in the mammary gland by stilbene estrogen, diethylstilbestrol (DES).

In the present study we have examined the effect of stilbene estrogen on the proliferative activity, cell cycle kinetics and the differentiation of the mammary gland of female Noble rats. The exposure of animals to stilbene estrogen (diethylstilbestrol) or natural estrogen (estrone) (10 micrograms/24 h) significantly increased proliferation in mammary epithelial cells. Both labeling index and growth fraction were increased by DES or estrone treatment. In addition, both stilbene and natural estrogen exposure altered cell cycle kinetics. Stilbene estrogen exposure to animals increased the conversion of mammary epithelial cells from G0 to G1 and G1 to S-phase cells by 8.3- and 8.5-fold, respectively, compared to that of control. Differentiation measured by the degree of lobular maturation revealed that the conversion of immature structures to mature structures was significantly increased by 2.4-fold in response to DES or estrone exposure compared to that of control. Perturbation of cell cycle is considered as a risk factor for the development of cancer. Changes in proliferation and cell cycle have been shown to lead to genetic instability, ultimately resulting in cell transformation. Our results indicated an increase in labeling index and growth fraction and a perturbation in cell cycle kinetics from DES or estrone exposure. Perturbation of cell cycle in response to stilbene estrogen exposure may produce adverse effects in the mammary glands of the Noble rats.

Animals↗

PubMed1995

In vitro conversion of environmental estrogenic chemical bisphenol A to DNA binding metabolite(s).

In the present study we have investigated the ability of bisphenol A to be converted to reactive metabolite(s) and its potential to bind to DNA. In this in vitro study we show that bisphenol A is oxidized by 70% to bisphenol o-quinone. The evidence for the formation of bisphenol o-quinone was shown by UV, IR and GC-MS. The new product, bisphenol o-quinone, had a maximum UV absorption at 386 nM, the appearance of an IR characteristic of unsaturated carbonyl (1690 cm-1) and a mass of 242. The chemical reaction of deoxyguanosine monophosphate (dGMP) or DNA with bisphenol o-quinone produced 6-8 adducts. The in vitro incubation of DNA with bisphenol A in the presence of peroxidase activation system also produced one major and seven minor adducts. The chromatographic mobilities of major DNA adducts four and six formed by bisphenol A in the presence of peroxidase activation system closely matched those of spots four and six obtained by chemical reaction between DNA or dGMP with bisphenol o-quinone. Based on these data it appears that bisphenol A is converted to DNA binding metabolites in vitro. Whether irreversible binding of bisphenol A to DNA through metabolic activation may be responsible for some of the toxic effects produced by bisphenol A is not clear.

Benzhydryl Compounds↗

PubMed1995

In vivo binding of diethylstilbestrol to nuclear proteins of kidneys of Syrian hamsters.

We demonstrate here that stilbene estrogen (diethylstilbestrol) is converted to nuclear protein binding metabolite(s) both in vitro and in vivo. In vitro reaction of DES with nuclei from hamster liver or kidney in the presence of cumene hydroperoxide or NADPH revealed binding of [3H]DES in nuclear proteins (histones; nonhistones precipitable by 2% TCA, NH2; nonhistones soluble in 2% TCA, NH30). The binding was significantly inhibited by cytochromes P450 inhibitors. In an in vitro system [3H]DES quinone, one of the metabolites of DES, was able to bind to pure nonhistone proteins RNA polymerase and DNA polymerase. The binding of [3H]DES quinone to nonhistones RNA polymerase and DNA polymerase was inhibited by low molecular weight thiols, i.e. glutathione and cysteine, or thiol modifiers, such as n-ethylmaleimide, dithionitrobenzoic acid and hydroxymercuric benzoate. DES and DES metabolites inhibited transcriptional activity. In vivo [3H]DES was able to bind to nuclear proteins of hamster liver, kidneys and testes. The level of in vivo [3H]DES binding to all three types of nuclear proteins (histones, NH2, NH30) in the kidney (target organ) was two or more fold higher than that observed in the liver or testis (nontarget organs). Four nuclear NH30 proteins (mol wts.: 56, 37, 33 and 28 kDa) were irreversibly bound to [3H]DES in vivo. The in vivo binding of [3H]DES to transcriptionally active chromatin NH30 proteins also was observed. The data reported here establish that DES was able to bind to liver or kidney nuclear proteins in vitro, which was catalyzed by nuclear enzymes when fortified with an appropriate cofactor. DES quinone may be one of the protein binding metabolites. DES and DES metabolites inhibited transcriptional activity. The level of in vivo binding of [3H] DES to nuclear proteins of kidney (target organ) was double in comparison with that observed in liver or testis (nontarget organs). In vivo modifications in the chromatin proteins may be a factor in the development of DES-induced renal carcinogenesis is not clear.

Animals↗