Randomization of Animals by Computer Program for Toxicity Studies

Martin, Ronald A.; Daly, Alan M.; DiFonzo, C.J.; Iglesia, Felix A. de la

doi:10.3109/10915818409009068

Cited by 42 publications

(20 citation statements)

References 12 publications

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“…Following quarantine for seven days, mice were randomized using a weight stratification method (Martin et al 1984) into two groups of thirty mice each: group 1 was fed basal diet only; group 2 was fed a diet containing 170 ppm NaAs III (100 ppm As III ). All animals were sacrificed after two weeks of treatment.…”

Section: Methodsmentioning

confidence: 99%

Inorganic Arsenic–Induced Intramitochondrial Granules in Mouse Urothelium

et al. 2008

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Based on epidemiological data, chronic exposure to high levels of inorganic arsenic in the drinking water is carcinogenic to the urinary bladder of humans. Recently, models have been developed involving transplacental administration of inorganic arsenic and subsequent administration of another substance that produces a low incidence of urogenital neoplasms. Administration of arsenite or arsenate in the diet or drinking water to fiveto eight-week-old mice or rats rapidly induces urothelial cytotoxicity and regenerative hyperplasia. In mice administered arsenite, we observed eosinophilic intracytoplasmic granules present in the urothelial cells. These granules were not present in urothelial cells of untreated mice or in treated or untreated rats. By transmission electron microscopy, the granules were located within the mitochondrial matrix, that is, mitochondrial inclusions. Arsenic, primarily as arsenite, was present in partially purified mitochondria containing these granules. Cells containing the granules were not usually associated with degenerative changes. Lack of these granules in rats suggests that they are not necessary for inorganic arsenic-induced urothelial cytotoxicity or hyperplasia. These granules have also been observed with exposures to other metals in other tissues and other species, suggesting that they represent a protective mechanism against metal-induced toxicity.Keywords: mitochondrial granules; urinary bladder; arsenite; cytotoxicity; hyperplasia diethylstilbestrol or tamoxifen, some eventually develop urogenital neoplasms. Furthermore, Simeonova et al. (2000) demonstrated that As III administered in the drinking water (0.01%) to C57BL x BDA2 mice for four weeks produced evidence of urinary bladder urothelial simple hyperplasia.In a previous short-term study involving administration of arsenate (As V ) in the drinking water to rats, we also observed urothelial hyperplasia (Lu et al. 2007). In subsequent experiments involving administration of As III and As V to mice, we noticed the presence of intracytoplasmic eosinophilic granules in the mouse urothelium, especially in the superficial cell layer (Suzuki et al. in press). In the present study we examined this phenomenon in greater detail in urothelial cells of mice administered As III . By transmission electron microscopy (TEM), we demonstrated that the granules are within the mitochondria. The urothelium in these mice also showed evidence of hyperplasia. Interestingly, in contrast to mice, treatment of rats with 200 mg/L sodium arsenite (NaAs III ) in the food did not produce mitochondrial granules (MG) despite detection of simple hyperplasia in the urinary bladder epithelium. MG have been observed in various tissues in different species subjected to exposure to certain heavy metal cations. The granules are mainly associated with the mitochondrial inner membrane and contain the metal within the matrix of the mitochondria (Brown et al. 1985;Jacob et al. 1994). The mitochondrion is an INTRODUCTION

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Section: Methodsmentioning

confidence: 99%

Inorganic Arsenic–Induced Intramitochondrial Granules in Mouse Urothelium

et al. 2008

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“…Ideally, methods for minimizing bias in the assignment of animals to study groups should be used. One such method is to randomize (Martin et al 1986), using both age and weight considerations with rigorous restraints on acceptance criteria.…”

Section: Choice Of the Rodent Modelmentioning

confidence: 99%

Laboratory Animal Science Issues in the Design and Conduct of Studies with Endocrine-active Compounds

Everitt

Foster²

2004

ILAR Journal

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The use of rodent models for research and testing on endocrine-active compounds necessitates an awareness of a number of laboratory animal science issues to standardize bioassay methods and facilitate reproducibility of results between laboratories. These issues are not unique to endocrine research but are particularly important in this field due to the complexities and interdependencies of the endocrine system, coupled with the inherently sensitive and variable nature of physiological endpoints. Standardization of animal models and the control of animal environments depend on the establishment of strong scientific partnerships between research investigators and laboratory animal scientists. Laboratory animal care and use programs are becoming increasingly complex and are constantly changing, fueled in part by technological advances, changes in regulations concerning animal care and use, and economic pressures. Since the early 1980s, many institutions have moved to centralization of animal facility operations concomitant with numerous changes in housing systems, barrier concepts, equipment, and engineering controls of the macro- and microenvironment. These and other changes can have an impact on animals and the conduct of endocrine experiments. Despite the potential impact of animal care and use procedures on research endpoints, many investigators are surprisingly naive to the animal facility conditions that can affect in vivo studies. Several key animal care and use issues that are important to consider in endocrine experiments with rodent models are described.

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“…Ar chiving of individual animal data is done for several reasons: (1) to maintain a per manent (magnetic-media) record of the study's data; (2) to provide data back-up; and (3) to allow data collection and re porting at various time intervals. The original system as purchased did not allow for the collection and reporting of more than one time period at the same time.…”

Section: Group Summary Reportsmentioning

confidence: 99%

“…We have previously described a com puter program for the randomization of animals into experimental groups of toxic ity studies (2). We have also reported on the development and implementation of automated data acquisition systems for recording clinical signs, body weights, food consumptions, drug intakes, organ weights, and gross and microscopic pa thology findings in toxicologic studies (3).…”

mentioning

confidence: 99%

A Microcomputer-Based Data Acquisition and Reporting System for Clinical Pathology Data from Animal Drug Toxicology Studies

Daly

Martin²,

McGuire³

et al. 1989

Drug Information Journal

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A microcomputer-based system has been developed for the acquisition, reporting, and evaluation of clinical biochemistry and hematologic data. The system consists of an IBM microcomputer interfaced with several peripheral devices. Associated com puter programs were developed inhouse and customized for use in animal drug toxicity studies. The system has the following advantages: (1) Data are directly transmitted to the microcomputer via interface devices, thereby minimizing the pos sibility of data entry errors and eliminating the need for handwritten records; (2) individual animal reports and group summary reports are readily generated; (3) individual animal data and group summary values are routinely compared during the data collection phase against a historical reference range database, and "outliers" are flagged, allowing quick identification of aberrant values or parameters that may have been affected by experimental treatments; and (4) treatment groups are tested in the data evaluation phase against control groups for statistically significant differ ences, which are automatically flagged in the summary tables. This microcomputer system has also assisted in Good Laboratory Practice audits and quality control monitoring.ALTHOUGH computer systems for han dling clinical pathology data from pa tients in a hospital setting have been exten sively developed, computer systems to meet the unique requirements of clinical

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Randomization of Animals by Computer Program for Toxicity Studies

Cited by 42 publications

References 12 publications

Inorganic Arsenic–Induced Intramitochondrial Granules in Mouse Urothelium

Inorganic Arsenic–Induced Intramitochondrial Granules in Mouse Urothelium

Laboratory Animal Science Issues in the Design and Conduct of Studies with Endocrine-active Compounds

A Microcomputer-Based Data Acquisition and Reporting System for Clinical Pathology Data from Animal Drug Toxicology Studies

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