bluuebunny/crossref_metadata_2025 huggingface dataset:
Exposure to Community Violence and Young Adult Crime: The Effects of Witnessing Violence, Traumatic Victimization, and Other Stressful Life Events
Authors: Eitle David , Turner R. Jay
Published: April 2009

Evidence has accumulated that young people in America are witnesses to considerable violence at home and in the community. This study is the first to examine the association between witnessing community violence and criminal behavior in a representative sample of young adults. In addition, the authors consider whether receiving traumatic news, witnessing domestic violence, experiencing accidents, and being the direct victim of domestic and community-based violence are independently associated with young adult crime. The results indicate that recent exposure to violence in the community along with a history of receiving traumatic news, direct victimizations in the community, recent life events, and associations with criminal peers increase the risk for young adult criminal offending. The implications of these results are discussed.
Developing a Typology for Understanding Visiting Friends and Relatives Markets
Authors: Moscardo Gianna , Pearce Philip , Morrison Alastair , Green David , O’Leary Joseph T.
Published: April 2009

This study seeks to classify visiting friends and relatives (VFR) travel and to explore the linkage between VFR travel types and commercial tourism in an empirical study. The VFR phenomenon is multifaceted, making it hard to integrate research findings. This article proposes an initial typology of VFR travel and positions the major existing studies within this typology. Using data from Queensland, Australia, an examination is made of the relationships between the proposed variables and VFR travel and behavior patterns. The data set gave the researchers the ability to identify VFR as either a prime trip motive or one of a set of activities or regional attractions. The study provides an activities-based segmentation of this type of VFR traveler and attempts to connect different segments to both travel patterns and the variables in the proposed typology.
Preparing for the New Economy: Advertising Strategies and Change in Destination Marketing Organizations
Authors: Gretzel Ulrike , Yuan Yu-Lan , Fesenmaier Daniel R.
Published: April 2009

Information technology, especially the World Wide Web, has had a tremendous impact on the tourism industry over the past years. It is difficult for most destination marketing organizations, however, to keep pace with the evolution of new technologies, the emergence of innovative advertising strategies, the changes in the consumer market, and the growing competition due to increasing globalization. The National Laboratory for Tourism and eCommerce organized a workshop in an effort to identify effective strategies for tourism advertising on the Internet. The results indicated that information technology has led to a number of profound changes in the assumptions underlying communication strategies. It was concluded that the change occurring in the new economy involves a rethinking of who partners and competitors are and how networks with other organizations can increase organizational capacity to learn. Thus, it is argued that success of destination marketing organizations in the new economy is more about change in approach than technology itself.
An Examination of the Determinants of Entertainment Vacationers’ Intentions to Revisit
Authors: Petrick James F. , Morais Duarte D. , Norman William C.
Published: April 2009

This study investigated the relationship of entertainment travelers’ past vacation behavior, vacation satisfaction, perceived vacation value, and intentions to revisit and repurchase. Subjects were inquirers for the purchase of an entertainment package that visited the destination and were systematically selected over a 12-month period. Results suggest that past behavior, satisfaction, and perceived value are good predictors of entertainment vacationers’ intentions to revisit the destination. It was further found that the variables of past behavior, satisfaction, and perceived value are poor predictors of intentions to visit and attend live theater entertainment or book an entertainment package during a visit. Given the relationships between past behavior, satisfaction, perceived value, and intentions to revisit, results of the present study provide important theoretical implications and direction for entertainment destination management.
What Do University-Educated Women Want from Their Pleasure Travel Experiences?
Authors: Pennington-Gray Lori A. , Kerstetter Deborah L.
Published: April 2009

This study focused on the benefits sought by university-educated women who travel for pleasure. Twenty-seven benefit statements were derived through a literature review and chosen a priori to represent nine separate benefit dimensions. A principal components analysis was used to reduce the data into benefit dimensions. Based on an outcome of nine benefit dimensions, not all of which met the a priori assumptions, cluster analysis was employed to identify similar “types” of respondents. The findings showed that there are three possible types of female travelers: rest and relaxation seekers, family/social seekers, and action seekers. When differences between the types of travelers were addressed, only employment status proved to be significant. Family/social seekers were more inclined than the other groups to be composed of working women.
Economic Benefits of Sport Fishing and Angler Wildlife Watching in Pennsylvania
Authors: Upneja Arun , Shafer Elwood L. , Seo Wonseok , Yoon Jihwan
Published: April 2009

This article answers two major policy questions about the economic benefits of sport fishing in the commonwealth of Pennsylvania: (1) what is the annual value of the common-wealth’s sport fishing resources, and (2) what is the annual impact from the use of that resource? The study also evaluates the nonconsumptive value of nonresidential wild-life-watching resources for angler households. A mail survey was used to collect data on licensed Pennsylvania anglers’ annual equipment and trip expenditures for sport fishing and for wildlife watching. Results of the travel cost method showed that the annual values of the sport fishing resources and the wildlife-watching resources were $3.98 and $0.50 billion, respectively. Results of the Impact Analysis for Planning model indicated that the annual economic impact of sport fishing was $4.75 billion. This information can be used with biological data, results of public opinion, and surveys about fisheries management to formulate policy decisions that help match availability of sport fishing resources with future demand.
A Guide for Undertaking Economic Impact Studies: The Springfest Example
Authors: Crompton John L. , Lee Seokho , Shuster Thomas J.
Published: April 2009

This study’s intent is to offer a generalizable model for undertaking economic impact studies that tourism professionals can use to conduct similar studies in their own communities. A conceptual rationale for undertaking economic impact studies is described. The four principles central to the integrity of economic impact analyses are reviewed: exclusion of local residents, exclusion of “time-switchers” and “casuals,” use of income rather than sales output measures of economic impact, and correct interpretation of employment multipliers. The economic impact of a festival on Ocean City, Maryland, is offered as an exemplar.
Macro Effects of Tourism in Victoria, Australia: A Nonlinear Input-Output Approach
Authors: West Guy , Gamage Ari
Published: April 2009

This article assesses the economic impacts of tourism on the Victorian economy in Australia using a modified version of the input-output model in which the linearity assumption is partially relaxed. The results indicate that in 1993-1994, in gross terms, day-trippers contributed the greatest amount to gross state product, followed by interstate, intrastate, and international visitors. If substitution expenditure effects by residents are taken into account, interstate tourism contributed the greatest amount to gross state product and employment, followed by international visitors. Per dollar of visitor expenditure, the Victorian government should promote interstate tourism for employment creation, although still encouraging international tourism for value adding.
Factors for Success in Rural Tourism Development
Authors: Wilson Suzanne , Fesenmaier Daniel R. , Fesenmaier Julie , Van Es John C.
Published: April 2009

Since the 1970s, economic restructuring and the farm crisis have reduced rural communities’ economic opportunities. These changes have limited rural communities’ economic development options, making older development strategies less viable and forcing many to look for nontraditional ways to sustain themselves. One of the most popular nontraditional rural development strategies has been tourism and its associated entrepreneurship opportunities because of tourism’s ability to bring in dollars and to generate jobs and support retail growth. The purpose of this study was to identify and examine those factors that have helped rural communities successfully develop tourism and its entrepreneurship opportunities. Several focus groups were conducted with local businesspersons and leaders in six rural Illinois communities. The results clearly demonstrate the importance of the community approach to tourism development and that rural tourism development and entrepreneurship cannot work without the participation and collaboration of businesspersons directly and indirectly involved in tourism.
The Impact of Gender and Religion on College Students’ Spring Break Behavior
Authors: Mattila Anna S. , Apostolopoulos Yorghos , Sonmez Sevil , Yu Lucy , Sasidharan Vinod
Published: April 2009

The authors investigated the influence of gender and religion on health-risk behavior potentials and destination-related expectations of college students on spring break vacation using a random sample of 534 students from two U.S. universities. Results indicated that gender and religion had a significant impact on students’ potential to engage in health-risk behaviors during spring break as well as their choice of spring break destinations and their expectations for hospitality service quality and characteristics of the destinations. Important social marketing and public policy implications for the tourism and hospitality industry are discussed.
The Market for Space Tourism: Early Indications
Authors: Crouch Geoffrey I.
Published: April 2009

The development and growth of space tourism faces a number of hurdles. Producing credible and reliable estimates of market demand represents one of the most significant of these. This article examines the early indications of the market for space tourism based on the limited research conducted to date. It identifies several research challenges and considers methodological alternatives that might improve research findings.
Informal Marketing of Israel Experience Educational Tours
Authors: Cohen Erik H.
Published: April 2009

The Israel Experience educational tours attract participants primarily through informal marketing. Friends, family, and former participants are the most effective advertisers. Most participants are already connected to community networks through which informal marketing takes place. Those attracted through informal, personal channels are more satisfied with their tours than are those recruited through conventional mass media advertising.
International Students’ Image of Rural Pennsylvania as a Travel Destination
Authors: Chen Po-Ju , Kerstetter Deborah L.
Published: April 2009

This exploratory examination of the image international students have of rural tourism areas in Pennsylvania documents that they have distinct images and that their responses to them differ depending on travel behavior and sociodemographic variables.
Political Instability, War, and Tourism in Cyprus: Effects, Management, and Prospects for Recovery
Authors: Ioannides Dimitri , Apostolopoulos Yiorgos
Published: April 2009

This article examines the divergent fortunes of the tourist industry on the divided island of Cyprus and discusses the prospects for crisis management and recovery. The Greek-Cypriot state has witnessed an economic miracle because of rapid tourism development. Conversely, tourism in the northern Turkish-Cypriot part has struggled due to international boycotts. The prospects of a burgeoning Cypriot tourist industry can be seen only in the context of a demilitarized single island-nation with a restructured and diversified product. A competitive single Cypriot tourism product could bring the two communities closer and serve as a catalyst for unfolding Cyprus’s sustainable development potential.
Predicting Souvenir Purchase Intentions
Authors: Kim Soyoung , Littrell Mary A.
Published: April 2009

Structural equation modeling was used for predicting souvenir purchase intentions of 277 U.S. female tourists traveling to Mexico. The respondents evaluated five textile products and described their travel behaviors. Findings suggested a sequence of significant relationships between hedonic values, world-mindedness, recreational and ethnic tourism, attitude toward souvenirs, and purchase intentions.
Managing the Asian Financial Crisis: Tourist Attractions in Singapore
Authors: Henderson Joan C.
Published: April 2009

This article considers tourist attractions in Singapore and the consequences of the Asian financial crisis for operators within the context of crisis management theory. The range of visitor attractions in Singapore is identified, and the period of economic turmoil that began in the late 1990s is summarized together with an account of its impact on tourist activity. The results of a survey of leading attractions indicate the effect of the crisis on business, responses to it, and the application of crisis management planning. The analysis suggests both an absence of formal planning and the need for it given the nature of travel and tourism and its exposure to uncertainty, risk, and disaster. The study thus provides an insight into how attractions’ managers deal with a crisis, but its limitations are also recognized with the need for more thorough analysis conducted during a longer period of time as the crisis continues to develop.
Criminal Violence
Authors: Harris Grant T. , Rice Marnie E. , Lalumière Martin
Published: April 2009

The authors examined the interrelationships and the independent contributions of three major constructs associated with male criminal violence (neurodevelopmental insults, antisocial parenting, and psychopathy) using structural equation modeling. Subjects were 868 violent offenders assessed or treated at a maximum security psychiatric hospital. Results indicated that neurodevelopmental insults and psychopathy are not interrelated but are both directly and independently related to criminal violence, and antisocial parenting is related to both neurodevelopmental insults and psychopathy but has no direct relationship to criminal violence. These results are not consistent with a view of psychopathy as a disorder but are consistent with the view of psychopathy as an evolved life history strategy. Criminal violence has at least two separate developmental pathways originating very early in life, one involving neurodevelopmental damage and one involving psychopathy.
The Acts of the Apostles in Canonical Context
Authors: Wall Robert W.
Published: April 2009

The hermeneutical key to the Acts of the Apostles lies in its canonical rather than its original historical life setting. Acts is positioned in the Second Testament canon between (a) the gospels and (b) the letters as a commmentary on each of these collections. While the author of Acts may have intended to insure acceptance of the Pauline tradition within the evangelist's church, the canonizing community used Acts to insure acceptance not only of Paul but of the Jewish mission of James, Cephas and John within the universalist gentile church in which Paul had already largely triumphed. Thus, Acts is positioned to serve as the context within which the canonical conversation between the Pauline and non-Pauline collections is understood. Finally, within the canonizing community, the author's narrative, by being retitled "Acts" could be seen to recount the mighty deeds of the apostles who are then be taken as first among the witnesses to God's mighty deeds within the community that took its identity from them.
Matthew as a Second Testament Deuteronomy
Authors: Grassi Joseph A.
Published: April 2009

Matthew's phrase "this gospel of the kingdom" is not found elsewhere in the Second Testament. There are distinct signs that Matthew uses this expression in reference to his own document. This conclusion follows from a study of the parallels in Matthew to Deuteronomy as "this book of this law," a unique First Testament designation. Deuteronomy describes itself as a book to be placed beside the holy ark every time it was read to the people. Accordingly, it contained the living, authoritative voice of God from the fiery Mount Sinai. Thematic parallels in Matthew, especially to the mountain of authority, indicate that the Gospel's author likewise intended his book as this gospel of the kingdom to be read perpetually to the people as the living voice and teachings of the son of God.
Anamnesis and Absence in the Lord's Supper
Authors: Brawley Robert L.
Published: April 2009

The view that the Lord's supper dynamically activates the presence of Christ governs the sacramentalism of the majority of Christians. Allegedly, its roots are sunk in a biblical idea of memorial. This article challenges that assumption and gives evidence that the dominant modem sacramentalism is a development beyond the canonical Second Testament. It also discusses themes of the absence of the risen Christ that run along with themes of presence in the Second Testament, relates those themes to the history of human suffering, and suggests that a modem consensus sacramentalism should be intentionally more inclusive.
BTB Review of Current Scholarship: Israelite Settlement of Canaan a Peaceful Internal Process - Part 2
Authors: Gnuse Robert
Published: April 2009

Guided by archaeological research, traditional scholarly models for the Israelite settlement of Canaan, namely processes of infiltration, invasion and revolution have been gradually losing ground to models of peaceful settlement. Part 2 of this BTB Review of Current Scholarship reviews the more recent trend which emphasizes the evolutionary nature of cultural and religious development.
Risk Perception and Prototype Perception: Independent Processes Predicting Risk Behavior
Authors: Thornton Bill , Gibbons Frederick X. , Gerrard Meg
Published: April 2009

Three studies examined the relative influence of two social-cognitive processes, risk perception and prototype perception, on the willingness of young adults to engage in unprotected sex. In the first two studies, despite participants' expressed intentions to engage in protected sex, perceived risk and prototype perception processes were independently predictive of their willingness to engage in unprotected sex. In a third study, prototype perception and risk perception independently predicted willingness to engage in unprotected sex, which, in turn, predicted actual contraceptive behavior 6 months later. Although the two constructs have some commonality reflecting a social comparison basis, results from all three studies suggest that they embody some unique or independent processes that can be differentially elicited. Theoretical and practical implications of the results are considered.
Renal Transplacental Carcinogenicity of 3,3-Dimethyl-1-Phenyltriazene in Rats: Relationship of Renal Mesenchymal Tumor to Congenital Mesoblastic Nephroma and Intralobar Nephrogenic Rests
Authors: Frank Anthony A. , Heidel Jerry R. , Thompson Daniel J. , Carlton William W. , Beckwith J. Bruce
Published: April 2009

Exposure of rat embryos to 3,3-dimethyl-1-phenyltriazene (DMPT) results in numerous malformations, but the urogenital system is not affected. In contrast, exposure of rat fetuses to DMPT has been reported to result in renal neoplasms, which were not further classified. To better understand this discrepancy in organotropism of the teratogenic and transplacental carcinogenic processes, the present study was undertaken to characterize the neoplasms induced in rat fetuses exposed to DMPT in utero. Renal neoplasms and persistent mesenchyme were observed in 19.2 and 11.5%, respectively, of the offspring of rats treated with 1 mg DMPT/ kg body weight intraperitoneally on gestation days 16, 18, and 20. The majority of these renal lesions were observed in females. The renal neoplasms were mixtures of various types of mesenchymal tissue derivatives including smooth muscle and fibrous connective tissue. These neoplasms would be classified as renal mesenchymal tumors in rats. Brain neoplasms (numerous types), compound odontomas, and micrognathism were observed predominantly in male offspring from the same group. This treatment also resulted in decreased body weights, increased incidence of sudden loss of body weight, tremors and ataxia, and hypoplastic testes. Exposure to single intraperitoneal doses of DMPT on gestation day 20 did not produce a classic dose-response pattern: Minimal effects were observed with 10 mg DMPT/kg (occasional renal mesenchymal tumors and brain neoplasms), marked effects were observed with 30 mg DMPT/kg (lower incidence rate of most of the alterations observed with 1 mg/kg on gestation days 16, 18, and 20), and no effects were observed with 60 mg DMPT/kg. DMPT administered intraperitoneally at 1 mg/kg body weight on gestation days 16, 18, and 20 is an animal model of transplacental chemically induced renal neoplasms, which provide lesions with similarities to both intralobar nephrogenic rests and congenital mesoblastic nephroma of humans. Why the kidney is a carcinogenic target and not a teratogenic target remains unknown.
Studies of Skin Toxicity In Vitro: Dose-Response Studies on JB6 Cells
Authors: Jain Pramod T. , Fitzpatrick Michael J. , Phelps Patricia C. , Berezesky Irene K. , Trump Benjamin F.
Published: April 2009

There are many reasons for developing in vitro tests of toxicity including cost, speed, studies of mechanisms, and studies utilizing human cells and tissues. The present study focuses on the development of in vitro tests to predict in vivo toxicity by comparing them to data from the literature. A broad spectrum of model toxic compounds was evaluated for toxicity on mouse skin JB6 cells in culture. These included mercuric chloride, sodium lauryl sulfate, formaldehyde, dimethyl sulfoxide, benzoyl peroxide, and ionomycin, all of which have been proven to be positive in the Draize test or in cutaneous toxicity studies. Cell viability was evaluated every 15 min for up to 1 hr, and then after 24 hr of treatment using the Trypan Blue exclusion method; morphological changes were evaluated using phase-contrast and transmission electron microscopy. Dose-and time-dependent cell death and morphological changes were observed at concentrations ranging from 10-14 to 10-2M. Arbitrary rankings were assigned based on 1) IC 50 value estimated from the present data, and 2) in vivo toxicity reported in the Registry of Toxic Effects of Chemical Substances. Good correlation between in vitro and in vivo toxicity based on arbitrary rankings was observed. Thus, these findings suggest that the JB6 cell culture model can be used for predicting in vivo toxicity. In the future, it may be possible to utilize this system for the study of intracellular ionized calcium ([Ca2+]1), and the expression of oncogenes as early indicators of toxicity.
Subacute Toxicity of a Halogenated Pyrrole Hydroxymethylglutaryl-Coenzyme A Reductase Inhibitor in Wistar Rats
Authors: Sigler Robert E. , Dominick Mark A. , Mcguire Edward J.
Published: April 2009

Wistar rats received an hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, a halogenated pyrrole designated PD 123244-15, orally by gavage for 14 days at 10, 50, 150, 300, and 600 mg/kg. Doses of 150-600 mg/kg caused death and marked systemic toxicity involving stomach, esophagus, liver, gonads, lymphoid tissues, and skeletal muscle. Histopathologic findings included hyperkeratosis in esophagus and forestomach, increased hepatic mitotic activity, ovarian follicular necrosis, testicular atrophy and arrested spermatogenesis, and skeletal muscle necrosis and regeneration. Elevated serum aspartate aminotransferase correlated with muscle necrosis and hepatocellular damage. Marked systemic effects associated with high plasma concentrations were consistent with toxicity defined for other HMG-CoA reductase inhibitors, with the exception of pathologic alterations in the esophagus and ovaries. Direct mucosal irritation may have contributed to forestomach and esophageal lesions induced by this halogenated pyrrole.
Fluorosis in a Wild Cotton Rat (Sigmodon hispidus) Population Inhabiting a Petrochemical Waste Site
Authors: Paranjpe Madhav G. , Sundeep Chandra A.M. , Qualls Charles W. , Mcmurry Scott T. , Rohrer Michael D. , Whaley Max M. , Lochmiller Robert L. , Mcbee Karen
Published: April 2009

We have developed an in situ mammalian model for evaluating environmental contamination using wild cotton rats. In a series of experiments, 200 male cotton rats were captured during 4 collection periods (spring 1991 = 35; fall 1991 = 60; spring 1992 = 53; fall 1992 = 52). A total of 103 of these cotton rats were captured from control sites, and the remaining 97 were captured from an abandoned oil refinery. All sites were located in the vicinity of Cyril, Oklahoma. There were alterations in the incisors of cotton rats captured from the refinery site. Normal color of cotton rat incisors is deep yellow-orange, which is imparted by a pigment normally produced by ameloblasts. Grossly, the upper incisors of 37 of 97 rats and lower incisors of 54 of 97 rats were affected. The affected incisors were white, chalky, and thin with striations and erosions of the enamel. Microscopic examination revealed that there were dysplastic and necrotic changes in the ameloblasts. The bone fluoride levels were significantly higher in rats captured from the refinery as compared to the rats captured from the control sites.
Sequential Functional and Morphological Alterations During Hepatocarcinogenesis Induced in Rats by Feeding of a Low Dose of 2-Acetylaminofluorene
Authors: Stenbäck Frej , Gebhardt Rolf , Sirma Hussein , Garbay Jean-Marc , Williams Gary M.
Published: April 2009

The early cellular events in liver carcinogenesis were studied in Fischer-344 male rats that either were fed 200 ppm 2-acetylaminofluorene (AAF) for up to 10 wk or were fed the carcinogen for 8 wk followed by maintenance for an additional 24 wk. By 1 wk of exposure, AAF caused a reduction in the number of glutamine synthetase (GS)-positive centrilobular hepatocytes, an increase in DNA synthesizing hepatocytes in the central areas of the hepatic lobules, and a shift from multinucleated to mononucleated hepatocytes, although overt hepatocellular necrosis was not evident. By 3 wk, altered hepatocellular foci characterized by deficiencies in iron storage (IS-) and collagen production and by expression of gamma-glutamyl transferase (GGT+) and placental-type glutathione transferase (PGT+) activity appeared. Single PGT+ cells were also found. During continued exposure, foci increased in number, size, and total area with the increases escalating between 8 and 10 wk of exposure. Cessation of AAF exposure at 8 wk resulted in a slight decrease in the number of foci after a further 6 wk of maintenance, but with continued maintenance for another 6 and 12 wk, the number again increased. IS- characterized the majority of foci during carcinogen administration, whereas after cessation of exposure, GGT+ and PGT+ foci predominated. None of the foci were positive for GS. After AAF exposure for 10 wk, a few neoplasms developed and greater numbers occurred after maintenance for a further 24 wk of rats exposed for 8 wk. We conclude the following: (a) the low dose of AAF caused subtle alterations in function and proliferation of normal hepatocytes and converted hepatocytes into focus cells; (b) reduction of the GS+ area is a sensitive indicator of cytotoxicity of AAF; (c) the development of some foci at an early stage depends on a promoting action of AAF, which ceased when the carcinogen was withdrawn, allowing some foci to undergo reversion; (d) a strong linkage exists in expression of IS-, GGT+, and PGT+ in foci; (e) the carcinogenic process accelerates in the absence of any indication of increased cytotoxicity by AAF; and (f) under the conditions of this study, no GS+ foci, adenomas, and carcinomas were found, indicating that no carcinogen-induced expression of GS occurred in these lesions and that GS expression is not linked to other phenotypic abnormalities.
Relationship Between the Development of Pulmonary Fibrosis and Lung Tumors in Syrian Golden Hamsters Induced by N-methyl-N-nitrosourethane
Authors: Yasuhara Kazuo , Mitsumori Kunitoshi , Yoshimura Hiroyuki , Imazawa Takayoshi , Hayashi Shim-Mo , Onodera Hiroshi , Takahashi Michihito , Hayashi Yuzo
Published: April 2009

To cast light on the relationship between the development of pulmonary fibrosis and lung cancer, female Syrian golden hamsters were given 5 sc injections of 0.6 mg/animal of N-methyl- N-nitrosourethane (MNUR) at 2-wk intervals and then maintained without any treatment for 26 wk. Bronchiolo-alveolar cell tumors and hyperplasias, which were recognized from week 4 after termination of treatment, were each subdivided morphologically into 3 types. Bronchiolo-alveolar cell tumors included papillary tumors consisting of basophilic cells, papillary tumors consisting of clear cells, and papillary/solid tumors consisting of pleomorphic cells, with papillary tumors consisting of basophilic cells predominating. Bronchiolo-alveolar cell hyperplasias encountered were glandular metaplasia, simple hyperplasia, and papillary hyperplasia. Glandular metaplasia was the most common of the hyperplastic lesions. To some extent, all the proliferative lesions were associated with inflammatory cell infiltration, but this varied greatly. The rate for papillary tumors consisting of basophilic cells with connective tissue proliferation was 35%. Among the hyperplastic lesions, the cell prolif erative activity of papillary hyperplasia (12.5%) was significantly higher than in other hyperplastic lesions, suggesting that this lesion might be a preneoplastic change. None of the lung proliferative lesions showed any unequivocal immunoreactivity for the p53 protein. The present study suggests that most lung tumors may develop from pulmonary inflammatory lesions induced by MNUR, but the possibility that DNA injuries to the respiratory epithelial cells by MNUR may cause lung tumors cannot be precluded.
Phagocytosis of Fluorescent Beads by Rat Thyroid Follicular Cells (FRTL-5): Comparison with Iodide Trapping as an Index of Functional Activity of Thyrocytes In Vitro
Authors: Sagartz John E. , Ozaki Atsushi , Capen Charles C.
Published: April 2009

The ability of FRTL-5 rat thyroid follicular cells to engulf latex beads by phagocytosis was evaluated using flow cytometry and compared to iodide trapping in response to selected growth factors, second messengers, and chemicals. Cell suspensions were analyzed to determine the percentage of fluorescence-positive cells as well as the fluorescence intensity of positive cells. Phagocytosis was stimulated by forskolin, cholera toxin, 8-Br-cAMP, calcitriol, and transforming growth factor-β. In contrast, phagocytosis was inhibited by insulin, calcium, and aminotriazole, but not by sodium iodide. The results of this study showed that phagocytosis of latex beads was regulated in a manner similar to iodide trapping and could be altered by the addition of numerous compounds. Phagocytic activity was stimulated by both cAMP-dependent and cAMP-independent pathways. Flow cytometric evaluation of phagocytosis of fluorescent latex beads represents a simple, rapid, nonradioactive index of thyroid function in vitro.
Review Article: Strain as a Determinant Factor in the Differential Responsiveness of Rats to Chemicals
Authors: Kacew Sam , Ruben Zadok , Mcconnell Robert F.
Published: April 2009

The beneficial effects derived from the use of chemicals in agriculture, energy production, transportation, pharmaceuticals, and other products that improve the quality of life are clearly established. However, continued exposure to these chemicals is only advantageous in conditions where the benefit far outweighs toxic manifestations. By law, determination of risk of toxicity necessitates the use of laboratory animals to establish whether chemical exposure is safe for humans. To simulate the human condition, it is incumbent upon investigators to choose a species in which pharmacokinetic and toxicokinetic principles are established and resemble those of humans. Some of the advantages to the use of rat in chemical toxicity testing include (a) similarities in metabolism, anatomy, and physiological parameters to humans; (b) the short life span, especially for carcinogenesis study; (c) the availability, ease of breeding, and maintenance at a relatively low cost; and (d) the existence of a large database to enable comparison of present to reported literature findings. However, the choice of rat can be complicated by several factors such as sex, age, and nutrition, but especially strain, where currently there are over 200 different strains of rat known to exist. The aim of this review is to demonstrate that there are differences in the responsiveness of rat strains to chemicals and that the susceptibility observed is dependent on the tissue examined. It is evident that the genotype differs among strains, and this may be responsible for differences in sensitivities to chemicals. Awareness of strain as a factor in susceptibility to toxicant action needs to be taken into account in interpretation of relevance of risk of toxicity for humans.
Metabolic and Morphometric Changes in Small and Large Intestine in Rats Fed High-Fiber Diets
Authors: Stark Aliza , Nyska Abraham , Madar Zecharia
Published: April 2009

Structural modifications of the intestine following fiber intake may play an important role in the physiological effects induced by dietary fiber. The aim of this study was to examine possible mechanisms for the hypocholesterolemic effects of dietary fibers by evaluating both biochemical and morphometric parameters. Thirty male Sprague-Dawley rats were divided into 3 groups and fed either a fiber-free, 15% fiber high methoxy pectin, or 15% cellulose diet for a 4-wk period. Plasma cholesterol levels, hepatic enzyme activity, and fecal bile acid excretion were determined, and changes in the intestinal structure were evaluated. Daily fecal bile acid excretion was significantly higher in rats fed the pectin diet accompanied by elevated HMG-CoA reductase activity. Pectin feeding led to significant elongation of both the small and large intestine whereas cellulose only affected colon length. Computerized image analysis of intestinal cross-sections showed enlarged muscle area in the ileum and midcolon of pectin-fed rats and greater mucosal area in the colon. Circular muscle cell hypertrophy was also observed in the colon. In contrast, the effects of cellulose feeding were limited to elongation of the colon accompanied by muscle cell hypertrophy, and little effect on ileal morphology was documented. These data indicate that the hypocholestrolemic effects of pectin may be due to increased bile acid secretion accompanied by significant morphological changes in the ileum and colon.
Immunohistochemical Study of Rat Renal Interstitial Fibrosis Induced by Repeated Injection of Cisplatin, with Special Reference to the Kinetics of Macrophages and Myofibroblasts
Authors: Amate Jyoji Y , Ishida Akihiro , Tsujino Kumiko , Tatsumi Masashi , Nakatsuji Shunji , Kuwamura Mitsuru , Kotani Takao , Sakuma Sadashige
Published: April 2009

Progressive renal interstitial fibrosis occurs following tissue injury, resulting in chronic renal failure. In the fibrogenesis, macrophages are speculated to induce myofibroblasts producing matrix protein. The kinetics of these cells in renal fibrosis induced in rats by repeated injection of cisplatin (CDDP) (2 mg/kg body weight, once weekly) was investigated immunohistochemically. During the 10-wk injection period, epithelial damage of the proximal renal tubules in the corticomedullary junction was seen, followed by cystic dilation of the affected tubules. During the 8-wk recovery period following the seventh injection, the size of the dilated lumina was diminished and atrophic tubules lined by regenerating epithelial cells appeared. Morphometrical analysis revealed that fibrosis began to develop around the dilated renal tubules in the injection period and was more advanced in the following recovery period. Coinciding with development of fibrotic tissues, the number of α-smooth muscle actin-positive myofibroblasts was significantly increased in the areas compared to that of controls. In the injection period, despite a significant increase in myofibroblast number, an elevation of ED-1 (primary antibody)-positive macrophage number was not observed. In the recovery period, however, a significant elevation of macrophage number was noticed in markedly advanced interstitial fibrosis. This suggests that rapid expansion of the macrophage population, probably resulting from release from myelosuppression due to CDDP, might contribute in part to development of myofibroblasts, leading to the augmented fibrosis in the recovery period.
Promoting Effect of Monosodium Aspartate, But Not Glycine, on Renal Pelvis and Urinary Bladder Carcinogenesis in Rat Induced by N-Butyl-N-(4-Hydroxybutyl)nitrosamine
Authors: Kitamura Motokazu , Konishi Noboru , Kitahori Yoshiteru , Fukushima Yasumasa , Yoshioka Nobuaki , Hiasa Yoshio
Published: April 2009

Although the incidences were relatively low, hyperplasias of the renal pelvis and the urinary bladder have been observed in Fischer-344 (F-344) rats after both sodium aspartate and glycine treatments in long-term 2-yr bioassays. In the present study, the effects of these amino acids on development of N-butyl- N-(4-hydroxybutyl)nitrosamine (BBN)-initiated urinary lesions were investigated in male and female F-344/DuCrj rats. F-344 rats of both sexes, 6 wk old at the commencement, were given 0.05% BBN for 4 wk and then treated with one of the amino acids at a level of 5.0% in the drinking water for the following 36 wk. Proliferative lesions in the renal pelvis often associated with necrosis and mineralization were increased in the group treated with BBN followed by sodium aspartate, but not by glycine, in both sexes. The same group demonstrated higher incidences of urinary bladder tumors with increased urinary pH and sodium concentration and decreased creatinine and uric acid, but not accompanying crystallization. These results showed a clear promoting effect of sodium aspartate for urinary carcinogenesis in rats. The mechanisms of the effect on the renal pelvis and urinary bladder might be different.
The Effects of Diet, Ad Libitum Overfeeding, and Moderate Dietary Restriction on the Rodent Bioassay: The Uncontrolled Variable in Safety Assessment
Authors: Keenan Kevin P , Laroque Philippe , Ballam Gordon C. , Soper Keith A. , Dixit Rakesh , Mattson Britta A. , Adams Stephen P , Coleman John B.
Published: April 2009

Ad libitum (AL) overfeeding is the most significant, uncontrolled variable affecting the outcome of the current rodent bioassay. There is a highly significant correlation between AL food consumption, the resultant obesity and body weight, and low 2-yr survival in rodents. AL feeding of diets with lowered protein, metabolizable energy (ME), and increased fiber does not improve survival. Only dietary restriction (DR) of all diets tested significantly improves survival and delays the onset of spontaneous degenerative disease (i.e., nephropathy and cardiomyopathy) and diet-related tumors. Moderate DR results in an incidence of spontaneous tumors similar to AL-fed rats, but the tumors are found incidentally and do not cause early mortality. There is a decreased age-adjusted incidence of pituitary and mammary gland tumors in moderate DR-fed rats, but tumor growth time is similar between AL and DR rats with only a delay in tumor onset time seen in DR-fed groups. Moderate DR does not significantly alter drug-metabolizing enzyme activities nor the toxicologic response to 5 pharmaceuticals tested at maximum tolerated doses (MTDs). However, moderate DR-fed rats did require much higher doses of 4 additional pharmaceutical compounds before classical MTDs were produced. Toxicokinetic studies of 2 of these compounds demonstrated equal or higher steady-state systemic exposures to parent drug and metabolites in moderate DR-fed rats. Markers of oxidative stress (lipid peroxidation, protein oxidation) are decreased and cytoprotective anti-oxidant markers are preserved in moderate DR-fed rats. But moderate DR does not delay reproductive senescence in female rats. Only marked DR delays reproductive senescence compared to AL and moderate DR-fed female rats. These and other data indicate that moderate DR is the most appropriate method of dietary control for the rodent bioassay when used to assess pharmaceuticals for human safety and compounds for risk assessment.
Mechanistic Data and Risk Assessment of Selected Toxic End Points of the Thyroid Gland
Authors: Capen Charles C.
Published: April 2009

Many goitrogenic xenobiotics that increase the incidence of thyroid tumors in rodents exert a direct effect on the thyroid gland to disrupt one of several possible steps in the biosynthesis, secretion, and metabolism of thyroid hormones. This includes (a) inhibition of the iodine trapping mechanism, (b) blockage of organic binding of iodine and coupling of iodothyronines to form thyroxine (T4) and triiodothyronine (T3), and (c) inhibition of thyroid hormone secretion by an effect on proteolysis of active hormone from the colloid. Another large group of goitrogenic chemicals disrupts thyroid hormone economy by increasing the peripheral metabolism of thyroid hormones through an induction of hepatic microsomal enzymes. This group includes central nervous system-acting drugs, calcium channel blockers, steroids, retinoids, chlorinated hydrocarbons, polyhalogenated biphenyls, and enzyme inducers. Thyroid hormone economy also can be disrupted by xenobiotics that inhibit the 5'-monodeiodinase that converts T4 in peripheral sites to biologically active T3. Inhibition of this enzyme by FD&C Red No. 3 lowers circulating T3 levels, which results in a compensatory increased secretion of thyroid stimulating hormone (TSH), follicular cell hypertrophy and hyperplasia, and an increased incidence of follicular cell tumors in 2-yr or lifetime studies in rats. Physiologic perturbations alone, such as the feeding of an iodine-deficient diet, partial thyroidectomy, natural goitrogens in certain foods, and transplantation of TSH-secreting pituitary tumors in rodents also can disrupt thyroid hormone economy and, if sustained, increase the development of thyroid tumors in rats. A consistent finding with all of these goitrogens, be they either physiologic perturbations or xenobiotics, is the chronic hypersecretion of TSH, which places the rodent thyroid gland at greater risk to develop tumors through a secondary (indirect) mechanism of thyroid oncogenesis associated with hormonal imbalances.
Review Article: A Brief Review of Formaldehyde Carcinogenesis in Relation to Rat Nasal Pathology and Human Health Risk Assessment
Authors: Morgan Kevin T.
Published: April 2009

The 1980 report that inhaled formaldehyde induced nasal squamous cell carcinomas in rats had a significant societal impact and resulted in extensive research in the fields of rodent nasal pathology and human cancer risk assessment. This article presents an overview of the evolution of these events. It is concluded that the nasal passages of humans and rats are fundamentally identical biological target organs. Nevertheless, in the case of human health risk assessment, minor differences between these species may be critically important. Special attention should be paid to interspecies differences in nasal dosimetry and local metabolism; thus, chemical toxicity data derived from rats require careful interpretation when used for human risk assessments. In the case of formaldehyde, it is recommended that low-concentration (≤2 ppm airborne exposure) extrapolation, where no tissue damage is observed, be uncoupled from the responses at high concentrations (≥6 ppm), where epithelial degeneration, regenerative cell replication, and inflammation appear to be essential driving forces in formaldehyde carcinogenesis. The presence of treatment-related nasal lesions in rats following exposure to chemicals should always be treated as an indication of a potential human health risk, whether exposure is by the inhalation, oral, or dermal route.
Carcinogenic Activity of the Flame Retardant, 2,2-Bis(bromomethyl)-1,3-Propanediol in Rodents, and Comparison with the Carcinogenicity of Other NTP Brominated Chemicals
Authors: Dunnick June K. , Heath James E. , Farnell Daniel R. , Prejean J. David , Haseman Joseph K. , Elwell Michael R.
Published: April 2009

Several brominated chemicals have been shown to be multisite-multispecies carcinogens in laboratory animals, and in this paper we report that the flame retardant, 2,2-bis(bromomethyl)-1,3-propanediol (BMP) is also a multisite carcinogen in both sexes of Fischer 344 rats and B6C3F, mice. BMP was administered continuously in the diet for up to 2 yr to rats at doses of 0, 2,500, 5,000, or 10,000 ppm and to mice at doses of 0, 312, 625, or 1,250 ppm. Interim groups of rats were examined at 15 mo. An additional recovery group of male rats received the chemical for 3 mo at 20,000 ppm in the feed, and then the control diet for the remainder of the study. Chemical exposure caused neoplasms of the skin, subcutaneous tissue, mammary gland, Zymbal's gland, oral cavity, esophagus, forestomach, small intestine, large intestine, mesothelium, kidney, urinary bladder, lung, thyroid gland, seminal vesicle, hematopoietic system, and pancreas in the male rat; mammary gland, oral cavity, esophagus, and thyroid gland in the female rat; lung, kidney, and Harderian gland in male mice; and subcutaneous tissue, lung, and Harderian gland in the female mouse. The recovery group of male rats presented with the same spectrum of treatment-related neoplasms as in the core study. In this recovery group, BMP (at 20,000 ppm) caused irreversible effects at numerous sites after 90 days of exposure that was not detectable by histologic examination, but without further exposure resulted in carcinogenic responses at 2 yr. BMP is mutagenic in the salmonella test, but it was not determined if the BMP-induced effects that eventually lead to development of neoplasms at multiple sites are the same in both species and in all organ systems affected.