David C. Mulligan, M.D., F.A.C.S.
Verapamil dosages: 240 mg, 120 mg, 80 mg
Verapamil packs: 30 pills, 60 pills, 90 pills, 120 pills, 180 pills, 270 pills, 360 pills
Endocrine disruptors: A missing link in the pandemy of type 2 diabetes and obesity Challenges of studying drugs in pregnancy for off-label indications: Pravastatin for preeclampsia prevention blood pressure vitamin d safe 80 mg verapamil. Prescriptions for contraindicated category X drugs in pregnancy among women enrolled in TennCare. Cellular mechanisms underlying failed beta cell regeneration in offspring of protein-restricted pregnant mice. In utero exposure to maternal tobacco smoke and subsequent obesity, hypertension, and gestational diabetes among women in the MoBa cohort. Fluoxetine-induced pancreatic beta cell dysfunction: New insight into the benefits of folic acid in the treatment of depression. Fetal exposure to sertraline hydrochloride impairs pancreatic beta cell development. Prenatal exposure to persistent organic pollutants and organophosphate pesticides, and markers of glucose metabolism at birth. Comparison of inhibition of glucose-stimulated insulin secretion in rat islets of Langerhans by streptozotocin and methyl and ethyl nitrosoureas and methanesulphonates. Cytokine production by islets in health and diabetes: Cellular origin, regulation and function. Cell-specific expression of the rat insulin gene: Evidence for role of two distinct 50 flanking elements. Defective catabolism of D-glucose and L-glutamine in mouse pancreatic islets maintained in culture after streptozotocin exposure. Preferential reduction of insulin production in mouse pancreatic islets maintained in culture after streptozotocin exposure. The role of depression and anxiety in onset of diabetes in a large population-based study. Dimethylurea: A radical scavenger that protects isolated pancreatic islets from the effects of alloxan and dihydroxyfumarate exposure. Inhibition of alloxan action in isolated pancreatic islets by superoxide dismutase, catalase, and a metal chelator. Impaired insulin release after exposure of pancreatic islets to autooxidizing dihydroxyfumarate.
Gamma Hydroxybutyric Acid Lactone (Gamma Butyrolactone (Gbl)). Verapamil.
Source: http://www.rxlist.com/script/main/art.asp?articlekey=96796
Immunobiology and immunopathology of human gut mucosa: Humoral immunity and intraepithelial lymphocytes pulse pressure of 100 240 mg verapamil purchase free shipping. Human mucosal addressin cell adhesion molecule-1 is preferentially expressed in intestinal tract and associated lymphoid tissue. Oral tolerance, food allergy, and immunotherapy: Implications for future treatment. All-trans retinoic acid enhances murine dendritic cell migration to draining lymph nodes via the balance of matrix metalloproteinases and their inhibitors. Lamina propria macrophages and dendritic cells differentially induce regulatory and interleukin 17producing T cell responses. T cell interleukin-17 induces stromal cells to produce proinflammatory and hematopoietic cytokines. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Review article: serotonin receptors and transportersdroles in normal and abnormal gastrointestinal motility. The role of epithelial Toll-like receptor signaling in the pathogenesis of intestinal inflammation. Identification of multiple isolated lymphoid follicles on the antimesenteric wall of the mouse small intestine. Inflammatory bowel disease: epidemiology, pathogenesis, and therapeutic opportunities. Microbial colonization influences composition and T-cell receptor V beta repertoire of intraepithelial lymphocytes in rat intestine. Interleukin-13 is the key effector Th2 cytokine in ulcerative colitis that affects epithelial tight junctions, apoptosis, and cell restitution. Th1- and Th2-cell commitment during infectious disease: asymmetry in divergent pathways. Generation of gut-homing T cells and their localization to the small intestinal mucosa. Recent progress in understanding the phenotype and function of intestinal dendritic cells and macrophages. Direct demonstration in intestinal secretions of an IgA memory response to orally administered Shigella flexneri antigens. The greater chemotactic network for lymphocyte trafficking: Chemokines and beyond. Homeostatic regulation of intestinal epithelia by intraepithelial gamma delta T cells.
Hyperemia Active increased localized blood flow to an area blood pressure medication sore joints purchase verapamil 240 mg with amex, particularly as a part of inflammation. Ischemia Interruption of blood supply to a tissue, with resulting damage due to lack of oxygen and nutrients. Karyorrhexis Fragmentation of the nucleus, can be evidence of apoptosis or necrosis. Metaplasia Reversible alteration of one differentiated cell type to another differentiated cell type, typically in response to chronic insult. Pyknosis Shrinking of the nucleus with condensation of chromatin, evidence of cell death. Stricture/stenosis Annular constriction due to circumferential fibrosis and contraction. Toll-like receptors A family of receptors involved in the recognition of components of pathogens, important in the innate immune response. This is slightly different from ulcers of the skin, where the breach is of the basement membrane underlying the epidermis. Oddly, many toxicology texts skip this system altogether or only discuss it in the context of carcinogenesis! However, if the offending toxin is not removed, perforation with peritonitis, scarring, and stricture, or mucosal hyperplasia, metaplasia, dysplasia, and neoplasia may result. Toxic exposure may also lead to functional but, not structurally visible abnormalities. However, as this chapter focuses on pathologic lesions, these scenarios will not be explored here. This proliferation is highly protective against many toxic mechanisms in that injured or altered cells are rapidly replaced. This characteristic render this cell population exquisitely more sensitive to radiation and radiomimetic toxins than those in other organs. Therefore, toxic damage to this barrier may lead to serious complications, such as disseminated bacterial spread (sepsis), with resulting shock. Interference with intestinal absorption can also lead to severe dehydration and malnutrition. The esophagus forms a tightly controlled passageway between the oral cavity and the stomach. In a healthy human or animal with nonkeratinized esophageal squamous epithelium, the mucosal surface is light pinkish tan, smooth, and glistening. In animals with a keratinized mucosa, such as herbivores and rodents, this surface can be rough and white.
Since Hox genes are implicated in cell proliferation and differentiation (Duboule arteria bologna buy verapamil 80 mg otc, 1995; Thorsteinsdottir et al. Indeed, we have shown that cyclin D3 expression remains downregulated in Hoxa-10 mutant uteri during the initial period of proliferation of stromal cells destined for decidualization (Das et al. Furthermore, Hoxa-10 may influence uterine stromal responsiveness to P4 by regulating local gene expression required for proliferation. Our results show numerous plausible gene targets during antimesometrial decidualization, organized into six functional categories, including growth regulation, tissue remodeling, immunomodulation, metabolism, membrane transport, and signal transduction. While it is known that increased stromal cell proliferation is considered to be an initiator of decidualization, establishment of a full-grown functional decidualization appears to depend on both proliferation and differentiation. Overall, our current concept suggests that aberrant activities of the cell-cycle regulatory molecules enforce inhibition of stromal cell proliferation in Hoxa-10 mutant mice. However, blastocyst activation and implantation can be initiated by an injection of estrogen in the P4-primed uterus (Ma et al. The mechanisms by which estrogen mediates the processes of blastocyst activation and implantation are poorly understood. Delayed implantation also occurs during lactation after postpartum ovulation and fertilization of the egg (McLaren, 1968; Yoshinaga, 1961). Mustelids and marsupials also exhibit seasonal delayed implantation (Aitken and Johnson, 1977; McLaren et al. In contrast, this does not occur in the hamster, guinea pig, rabbit, and pig; whether this occurs in primates is not known. The delayed implantation models in mice and in other species could be exploited more extensively to better understand the molecular signaling that emanates from the embryo and influences uterine biology and vice versa. Implantation can be divided into three stages: apposition, adhesion, and penetration (Enders and Schlafke, 1967; Enders and Schlafke, 1969). These three stages of implantation are a continuous process over a period of time. The attachment reaction coincides with a localized increase in stromal vascular permeability at the site of blastocyst attachment (Psychoyos et al. The uterine luminal closure occurs during pregnancy or pseudopregnancy and thus does not require the presence of blastocysts.
In addition arteria omerale cheap 80 mg verapamil with amex, an individual growth factor can sometimes produce either proliferation or neuron-like differentiation, depending on its concentration (Powers et al. These observations suggest that messages converging at the exterior of a chromaffin cell utilize both parallel and convergent intracellular pathways to coordinate their effects. Toxic Responses of the Adrenal Medulla 193 Both strain- and age-dependent differences in adrenal medullary physiology have been described in rats. Under resting conditions, normal young adult rats of commonly studied strains apparently have comparable levels of plasma catecholamines. However, marked differences have been demonstrated between strains in response to stress (McCarty and Kopin, 1978). Some strain differences might reflect variations in cholinergic innervation of the adrenal medulla. The functional regulation of the rat adrenal medulla undergoes two age-dependent transitions, related predominantly to changes in innervation. The first occurs after the end of the first week of life, with the onset of splanchnic nerve activity. This period is marked by increases in catecholamine and neuropeptide synthesis (Coulter et al. Nerve activity in Wistar rats 400 days old is more than twice that of rats 100 days old (Ito et al. Age-related functional differences between strains or between males and females have not been extensively studied. However, age-related differences in the composition of chromaffin granules have been reported (Santer and Hann, 1993). Mitoses are readily identified in histological sections of postnatal rat adrenals, but are rare after the age of 60 days. Adult rat chromaffin cells were therefore regarded for many years as essentially postmitotic and terminally differentiated. However, they did not determine whether proliferation was restricted to a distinctive subset of cells. Cell kinetic studies based on incorporation of bromodeoxyuridine (BrdU) in vivo estimate a renewal rate of approximately 1% per day for adult rat chromaffin cells (Verhofstad, 1993). These and even larger differences might be attributable to differences in animal maintenance, such as group housing versus solitary housing (Tischler et al. Inter-experimental comparisons should therefore be made with caution, particularly for older studies without carefully controlled maintenance conditions. Chromaffin cell proliferation in adult rats has been shown to be stimulated by a short course of administration of reserpine, one of the many agents that induce adrenal medullary tumors after chronic administration (Tischler et al. Hypothetically, the mitogenic effect might serve to increase the functional reserve of the adrenal medulla in response to increased physiological demands.
Pesticide toxicity is a global problem; most poisonings are in developing countries (Bardin et al arterial insufficiency discount verapamil 80 mg online. The principal defenses against these factors are mucus production, bicarbonate secretion, and the phospholipid hydrophobicity of the surface epithelium (Allen and Garner, 1980; Hills et al. The adherent mucus gel enhances surface neutralization of acid by bicarbonate (Allen et al. When the bicarbonate and mucus cap are broken, gastric acid injures cells and destroys capillaries (Ivey, 1988). If the break in the defensive barrier is temporary, epithelial repair is rapid by adjacent cell migration. These reductions decrease mucus and bicarbonate secretion allowing hydrochloric acid and other luminal compounds to attack epithelial cells. Trefoil peptides likely play a role in maintaining mucosal integrity by enhancing intestinal cell migration following injury (Babyatsky et al. Trefoil peptides are present in high concentrations in the mucus gel of the mucosa. The mechanism is probably topical, suggesting that trefoil peptides interact with mucine glycoprotein to reinforce the mucus gel layer (Rachmilewitz, 1996). Trefoil peptides may protect against gastric damage induced by Helicobacter pylori. Pentavalent arsenate uncouples mitochondrial oxidative phosphorylation by competing with phosphate in the formation of adenosine triphosphate. Orally ingested arsenicals are taken up in high concentrations by intestinal epithelial cells and act intracellularly to disrupt energy production and enzyme activity. The surface epithelial cells poisoned with arsenic quickly exfoliate, denuding the villus epithelium. Epithelial rupture leads to exudation of plasma into the intestinal lumen where it coagulates. Movement of large volumes of fluid into the intestine produces distention that initiates propulsive contractions. Repair of the epithelium is impaired by the arsenic and significant intestinal blood loss may occur (Reddy and Hayes, 1989). Ingestion of ionic inorganic mercury leads to precipitation of mucosal proteins and a corrosive effect on the gastrointestinal mucosa. Acute mercury intoxication is characterized by sloughing of the epithelium and abdominal pain. Chronic lead intoxication produces gastrointestinal symptoms that are an important sign of exposure, especially in adults.
Syndromes
Hontela and Vijayan (2008) have recently reviewed the evidence of adrenocortical toxicity in fish and Blaha et al blood pressure range for men discount 240 mg verapamil amex. Fish are particularly vulnerable to the effects of pollutants because they are continuously exposed via the water (this continuous low-level exposure has the effect of lowering effective dose levels). However, more recently, birds have been reported to show impaired adrenal function. Exposure to these contaminants has been less direct and has shown accumulation up the food chain. The impact of impaired adrenocortical function and stress response in environmental species is much the same as in laboratory species and humans, and the consequence of reduced survival fitness in wildlife is obvious. The additional consideration with adrenocortical toxicity as a cause of demise in either an individual or a population is that it can be difficult to diagnose and often leaves no obvious external morphological clues, as is the case for estrogenic endocrine disruption and reproductive malformations. Baos and Blas (2008) review adrenocortical toxicology in birds with a particular emphasis on the effects of environmental contaminants and the avian stress response, which as described previously is a vital survival response and of particular importance to free-living wildlife. In terms of the impact of environmental exposures and human adrenocortical toxicity, it is not known whether human adrenocortical function has altered over the past few decades as suggested for sperm production and fertility due to estrogenic or 182 Toxic Responses of the Adrenal Cortex antiandrogenic endocrine disruptors. Consequently, the extent of human occult adrenal effects from environmental chemical exposures is unknown. The adrenal is a vital organ and dysfunction of the steroidogenic pathways for either glucocorticoid or mineralocorticoid production can result in significant morbidity and mortality. Adrenal hypertrophy/adrenocortical cellular hypertrophy are common findings in toxicity studies and also often incorrectly attributed to "stress": these findings should not be attributed to stress unless there is clear evidence that the adrenal cortex is also functional. Empirical evidence is required to support a stress mechanism and rule out direct adrenocortical toxicity, enzyme inhibition, or functional adrenocortical insufficiency. Finally, regulatory agencies are now recognizing the importance of the adrenal in "endocrine disruption" and validation of the H295R assay is currently underway, mainly because of its universal steroidogenic capabilities; however, a fully integrated evaluation strategy is required to properly evaluate this uniquely complex endocrine gland. Histopathology of preclinical toxicity studies: Interpretation and relevance in drug safety evaluation (3rd edn. The vulnerable brain and environmental risks, malnutrition and hazard assessment (pp. The first sees both the adrenal medullary cells and the agents that affect them as investigative tools, while the second focuses on adrenal medullary toxicity as an indicator of harm to the organism. The secretory cells of the adrenal medulla, known as chromaffin cells, are prototypical neuroendocrine cells. As such, they have been extensively utilized as a model for studying mechanisms that regulate cellular differentiation and function in both the endocrine and nervous systems (Diaz-Flores et al. Examples include marine toxins that block voltage-gated ion channels (Alvarez et al. These and other toxins have been employed to dissect mechanisms of hormone secretion by chromaffin cells (Maruta et al. However, in terms of whole animal toxicology, the effects of these toxins on chromaffin cells are inconsequential in view of their rapid and often lethal effects on the nervous system. Many attempts have been made to elucidate the mechanisms of neurotoxicity by pharmacological studies using chromaffin cells as an experimental model (Knoth-Anderson and Abou-Donia, 1993; Kujacic and Carlsson, 1994).
Earlier studies of human phase I metabolism of pesticides were summarized in 2001 and 2003 (Hodgson hypertension kidney failure generic verapamil 120 mg buy on-line, 2001, 2003) and an updated version of this database is in preparation. A more current summary of pesticide substrates for human hepatic xenobiotic-metabolizing enzymes is presented in Table 3. Conjugation reactions of pesticides are less well known although early studies have been reviewed (Dorough, 1984; Matsumura, 1985; Motoyama and Dauterman, 1980). Several of the conjugating enzymes are nonmicrosomal, particularly cytosolic, and catalyze various types of conjugation with pesticides as substrates. The C-6 glutathione conjugate of chlorpyrifos has also been detected in human hepatocytes (Choi et al. The conjugation products are typically further metabolized and, in humans, excreted as urinary mercapturic acids. Glucuronides are important metabolites of carbamates, including propamocarb (Banol), carbaryl, and carbofuran (Marshall and Dorough, 1979; Mehendale and Dorough, 1972), as well as some organophosphorus and other pesticides (Hutson, 1981). Ethereal sulfates, although not common in pesticide metabolism, may be formed from the oxidative metabolites of carbaryl and carbofuran (Dorough, 1968; Dorough, 1970). Methylation coupled to thiol-driven oxidation via activity of a methyltransferase is a major determinant of clearance of inorganic arsenic, such as used in legacy insecticides (Hughes et al. Although not strictly speaking a detoxication reaction, hepatic aliesterase, by forming a stable phosphorylated enzyme with organophosphates (oxons), may serve as an inert storage protein (Chambers et al. From their relative reactivity in recombinant expression systems, numerous pesticides have now been determined to be Metabolism and Hepatotoxicity of Pesticides Table 4 Human hepatic phase I xenobiotic-metabolizing enzymes active in pesticide studies Substrate Permethrin metabolite: phenoxybenzyl alcohol (Choi et al. In vitro human phase I metabolism of xenobiotics I: pesticides and related compounds used in agriculture and public health. Metabolism and Hepatotoxicity of Pesticides 547 ligands of nuclear receptors that regulate gene expression of various metabolic enzymes. Complementary information has been derived from toxicogenomic profiles of expression arrays for pesticides relative to that of prototype nuclear receptor activators (Tully et al. Although an increase in the amount of an enzyme can occur by decreasing the degradation rate, increasing the synthesis rate is the most common mechanism for induction by xenobiotics. Coordinate (pleiotypic) induction, the induction of multiple enzymes by a single inducing agent. Hepatocytes are the choice for the study of induction in humans while the human liver-derived HepG2 cell line is also frequently used. Variation between hepatocyte donors yields information on metabolic variation in the human population. The cultured HepG2 cell line is not variable and is the cell line of choice for the study of induction mechanisms (Westerink and Schoonen, 2007; Das et al. Thus, dose-response studies utilizing not only induction but also cytotoxicity as endpoints, are essential. Early experiments in surrogate animals, reviewed in Hodgson and Meyer (2010), confirmed hepatic enzyme induction, but methods for the identification of individual isoforms were not yet available and reliance was placed on assessment of enzyme activities. Accordingly, the pesticide was often classified as a phenobarbital, 3-methylcholanthrene, or mixed-type inducer.
Typically hypertension in dogs discount verapamil 120 mg online, this is seen microscopically as luminal crystalline iron adjacent to the surface epithelium, or admixed with luminal fibrino-inflammatory exudates, and erosive or ulcerative mucosal injury (Abraham et al. Kayexalate crystals display a characteristic mosaic pattern that resembles narrow, rectangular fish scales, and are refractile but not polarizable. The findings tend to be striking in the esophagus, with prominent mitotic arrest with ring forms, associated with epithelial necrosis and ulceration of the esophageal mucosa. Since it is impossible to separate the effects of these two medications with certainty on histological examination, clinical correlation is required. However, in contrast to taxol, colchicine toxicity is typically encountered in the antrum of the stomach and in the small bowel. Thus, the most important aspect of therapy is to make the correct diagnosis and then to avoid repeat injury with the drug. Acute corrosive injuries of the stomach: A single unit experience of thirty years. Therapeutic approach to caustic damage of the 1st segment of the digestive tube due to ingestion of strong acids and alkalies. Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. Should computerised tomography replace endoscopy in the evaluation of symptomatic ingestion of corrosive substances The pathology of experimentally produced lye burns and strictures of the esophagus. Results of a new technique in the treatment of severe esophageal stenosis in children: Poliflex stents. Caustic ingestion in adults: the role of endoscopic classification in predicting outcome. Computed tomography evaluation of high-grade esophageal necrosis after corrosive ingestion to avoid unnecessary esophagectomy. Polyunsaturated phosphatidylcholine lowers collagen deposition in a rat model of corrosive esophageal burn. The efficacy of single-dose 5-fluorouracil therapy in experimental caustic esophageal burn. Topical mitomycin C application is effective in management of localized caustic esophageal stricture: A double-blinded, randomized, placebo-controlled trial. Topical mitomycin C can effectively alleviate dysphagia in children with long-segment caustic esophageal strictures.
The model proposed for the horse is based on the pattern of stem cell renewal that has been proposed in classical studies of the rat (Huckins arrhythmia detection 240 mg verapamil buy mastercard, 1978), bull (Hochereau-de Reviers, 1981), boar (f), and ram (Ortavant, 1958). Developing flagella (F) from (A) Sa spermatids below the luminal surface project toward or (B) into the lumen. Scanning electron microscopy of the epithelium and spermatozoa in the equine excurrent duct system. These bridges between cells in the same developmental step result from incomplete cytokinesis during cell division. The intercellular bridges may function to facilitate synchronous development or degeneration of similar germ cells. Since the presence of intercellular bridges is among the earliest features of committed spermatogonia. Since germ cells arise as a clone from a single stem cell during spermatocytogenesis, a defect in this single cell could result in the loss (degeneration) of the entire progeny of the clone. Toxicants that alter mitosis or differentiation of spermatogonia are expected to have a significant influence on the total productivity and efficiency of spermatogenesis. Meiosis occurs only in germ cells (male and female), and in males these cells are spermatocytes. Following the mitotic division of B2 spermatogonia, preleptotene primary spermatocytes result. Genetic exchange occurs at the synaptonemal complex between paired chromosomes in zygotene and pachytene primary spermatocytes. In males, the X and Y chromosomes partially synapse, but this partial synapsis is sufficient to keep the X and Y chromosomes paired on the spindle for the first meiotic division (Alberts et al. The pairing of sex chromosomes not only ensures the segregation of these homologous chromosomes in meiosis but also ensures that spermatozoa each contain either one X or only one Y chromosome and not both X and Y or neither chromosomes (Alberts et al. During the first meiotic division, pachytene primary spermatocytes rapidly undergo metaphase (chromosomal alignment), anaphase (separation of chromosomes), and telophase (complete separation of chromosomes) to produce secondary spermatocytes. Histologically, these cells have spherical nuclei with chromatin profiles of varying sizes. Hence, one duplication of chromosomes followed by two divisions (reduction division and equatorial division) produces the haploid genomes of spermatids and spermatozoa. Spermatogenic potential could be altered by toxicants that alter the cell division process or exchange of genetic material during the long prophase of meiosis. Spherical cells with spherical nuclei change shape to form a streamlined head with a condensed nucleus, an acrosomal covering, and a tail that is necessary for cellular motility. In the spermatozoon, the acrosome is a membrane-bound enzyme-containing bag over the nucleus. The Golgi apparatus of new spermatids gives rise to the acrosome as it does to lysosomes in all cells.
Ur-Gosh, 62 years: Cretinism is usually taken to signify impaired fetal brain development as a consequence of maternal hypothyroidism but the condition also includes reduced bone growth, smallness for gestational age, and low basal metabolism in the infant (reviewed by Lazarus, 2011; Obian et al. Indeed, it is well known that bleeding as well as thrombosis is common in end-stage liver disease (Lisman et al. This is slightly different from ulcers of the skin, where the breach is of the basement membrane underlying the epidermis.
Ressel, 54 years: Derived Reference Doses (RfDs) for the environmental degradates of the herbicides alachlor and acetochlor: Results of an independent expert panel deliberation. Hydrolysis of pyrethroids by human and rat tissues: examination of intestinal, liver and serum carboxylesterases. Proceedings of the National Academy of Sciences of the United States of America, 101, 1650116506.
Runak, 41 years: Epidemiology and prevention of non-steroidal anti-inflammatory drug effects in the gastrointestinal tract. Recapitulation of the microenvironments and interactions of the various hepatic cell types within an isolated culture device alone will not result in a full reproduction and corresponding understanding of the action of a xenobiotic on the liver as presented to an animal or human in vivo. In the United States, the predominant source of perchlorate intake is food, whereas drinking water is a less frequent and far smaller contributor (Huber et al.
Seruk, 35 years: All changes observed at 3 h are more pronounced at 24 h after treatment, with the exception of alterations in sinusoidal endothelial cells, which return to normal. Molecular mechanisms of insulin-like growth factor-1 mediated regulation of the steroidogenic acute regulatory protein in mouse Leydig cells. Neonatal outcomes after prenatal exposure to selective serotonin reuptake inhibitor antidepressants and maternal depression using population-based linked health data.
Dolok, 53 years: In Monographs on the evaluation of carcinogenic risks to humans, dry cleaning, some chlorinated solvents and other industrial chemicals. In gossypol-treated rats, sperm morphology was compromised severely, but the epithelium in testis and epididymis appeared morphologically normal. Genetic and epigenetic changes in rat preneoplastic liver tissue induced by 2-acetylaminofluorene.
References