Female Cotton Rats Research Articles

Pulmonary function analysis in cotton rats after respiratory syncytial virus infection.

The cotton rat (Sigmodon hispidus) is an excellent small animal model for human respiratory viral infections such as human respiratory syncytial virus (RSV) and human metapneumovirus (HMPV). These respiratory viral infections, as well as other pulmonary inflammatory diseases such as asthma, are associated with lung mechanic disturbances. So far, the pathophysiological effects of viral infection and allergy on cotton rat lungs have not been measured, although this information might be an important tool to determine the efficacy of vaccine and drug candidates. To characterize pulmonary function in the cotton rat, we established forced oscillation technique in uninfected, RSV infected and HDM sensitized cotton rats, and characterized pulmonary inflammation, mucus production, pulmonary edema, and oxygenation. There was a gender difference after RSV infection, with females demonstrating airway hyper-responsiveness while males did not. Female cotton rats 2dpi had a mild increase in pulmonary edema (wet: dry weight ratios). At day 4 post infection, female cotton rats demonstrated mild pulmonary inflammation, no increase in mucus production or reduction in oxygenation. Pulmonary function was not significantly impaired after RSV infection. In contrast, cotton rats sensitized to HDM demonstrated airway hyper-responsiveness with a significant increase in pulmonary inflammation, increase in baseline tissue damping, and a decrease in baseline pulmonary compliance. In summary, we established baseline data for forced oscillation technique and other respiratory measures in the cotton rat and used it to analyze respiratory diseases in cotton rats.

Cotton rat (Sigmodon hispidus) develops metabolic disorders associated with visceral adipose inflammation and fatty pancreas without obesity.

Obesity induces metabolic disorders such as type 2 diabetes, hypertension, and cardiovascular diseases and has become a global health concern. Recent studies imply that fat accumulation in nonadipose tissue correlates with metabolic disorders. However, there are no suitable animal models to evaluate this phenomenon. This study investigated the characteristics of metabolic disorders found in cotton rat (Sigmodon hispidus). Blood biochemical examinations revealed that cotton rats, predominantly males, developed hyperinsulinemia, hyperglycemia, and dyslipidemia when fed a normal diet. The islets increased in size through β-cell hyperplasia, which was associated with serum insulin level in both sexes, strongly indicating insulin resistance. In male cotton rats, oxidative stress was observed in β cells, and macrophage infiltration into the visceral white adipose tissue was reported, both of which were associated with serum insulin level without visceral obesity. In contrast, female cotton rats developed hyperinsulinemia without histopathological changes that were reported in males. Adipocytes were found to be accumulated in the pancreas but not in the liver of both sexes during aging. Pancreatic fat accumulation was associated with the serum insulin level only in females. Taken together, cotton rats developed metabolic disorders associated with visceral fat inflammation in the absence of obesity. In addition, pancreatic ectopic fat may also be related to the early stages of these conditions. Thus, the cotton rat may serve as a novel and useful model for metabolic disorders characterized by visceral adipose inflammation and ectopic fat accumulation in the pancreas without obesity.

Close pathological correlations between chronic kidney disease and reproductive organ-associated abnormalities in female cotton rats.

Cotton rat ( Sigmodon hispidus) is a useful experimental rodent for the study of human infectious diseases. We previously clarified that cotton rats, particularly females, developed chronic kidney disease characterized by cystic lesions, inflammation, and fibrosis. The present study investigated female-associated factors for chronic kidney disease development in cotton rats. Notably, female cotton rats developed separation of the pelvic symphysis and hypertrophy in the vaginal parts of the cervix with age, which strongly associated with pyometra. The development of pyometra closely associated with the deterioration of renal dysfunction or immunological abnormalities was indicated by blood urea nitrogen and serum creatinine or spleen weight and serum albumin/globulin ratio, respectively. These parameters for renal dysfunction and immunological abnormalities were statistically correlated. These phenotypes found in the female reproductive organs were completely inhibited by ovariectomy. Further, the female cotton rats with pyometra tended to show more severe chronic kidney disease phenotypes and immunological abnormalities than those without pyometra; these changes were inhibited in ovariectomized cotton rats. With regard to renal histopathology, cystic lesions, inflammation, and fibrosis were ameliorated by ovariectomy. Notably, the immunostaining intensity of estrogen receptor α and estrogen receptor β were weak in the healthy kidneys, but both estrogen receptors were strongly induced in the renal tubules showing cystic changes. In conclusion, the close correlations among female reproductive organ-associated abnormalities, immunological abnormalities, and renal dysfunction characterize the chronic kidney disease features of female cotton rats. Thus, the cotton rat is a unique rodent model to elucidate the pathological crosstalk between chronic kidney disease and sex-related factors. Impact statement The increasing number of elderly individuals in the overall population has led to a concomitant age-related increase in chronic kidney disease. Moreover, the global prevalence of patients with chronic kidney disease is gradually increasing, which poses a serious public health problem. The limited number of spontaneous chronic kidney disease animal models, which resemble chronic kidney disease pathogenesis in elderly individuals, is a major limitation in the development of experimental and curative medicines for chronic kidney disease. This pathological study clarified that sex-related factors, including hormones, and abnormalities of the female reproductive system, such as pyometra, are closely associated with chronic kidney disease development by using cotton rats ( Sigmodon hispidus). Further, ovariectomy inhibited the phenotypes of the female reproductive system, immunological abnormalities, and chronic kidney disease. Thus, this laboratory rodent serves as a novel and useful spontaneous chronic kidney disease model to elucidate the candidate disease factors and the pathogenesis of chronic kidney disease both in human and experimental medicine.

Female cotton rats (Sigmodon hispidus) develop chronic anemia with renal inflammation and cystic changes.

The cotton rat (Sigmodon hispidus) is a laboratory rodent that has been used for studies on human infectious diseases. In the present study, we observed that female cotton rats, not the male cotton rats, developed chronic anemia characterized by reduced red blood cell, hemoglobin, and hematocrit levels from 5 to 9months of age without any changes in the mean corpuscular hemoglobin and volume levels. In peripheral blood, the reticulocyte count did not increase in response to anemia in female cotton rats, and no extramedullary hematopoiesis was observed in the liver or spleen. Further, the serum levels of urea nitrogen and creatinine increased from 5 to 9months of age in female cotton rats compared to male cotton rats, and these increases became more prominent from 10months of age onward, indicating chronic kidney disease. Histopathologically, female cotton rats manifested tubulointerstitial lesions characterized by the infiltration of mononuclear cells, including plasma cells and CD3(+) T-cells, as well as the dilation of calbindin-D28k(+) distal tubules from 5 to 9months of age. The severity of these lesions progressed from 10months of age onward, and renal fibrotic features and numerous tubular cysts appeared without any obvious glomerular lesions. A significant decrease in the erythropoietin protein levels was observed in the kidney of aged female cotton rats, and significant correlations were detected between anemia and tubulointerstitial damage. These results suggest that aged female cotton rats chronically develop renal anemia, and this rodent may serve as a novel model to elucidate its pathogenesis.

Maternal transfer of RSV immunity in cotton rats vaccinated during pregnancy

Respiratory Syncytial Virus (RSV) is the leading cause of pneumonia and bronchiolitis in infants, resulting in significant morbidity and mortality worldwide. There is currently no RSV vaccine. Although maternal serum antibodies against RSV are efficiently transferred through placenta protecting human infants from RSV-induced disease, this protection is short-lived and the methods for extending and augmenting protection are not known. The objective of this study was to develop an animal model of maternal RSV vaccination using the Sigmodon hispidus cotton rat. Naïve or RSV-primed female cotton rats were inoculated with live RSV and set in breeding pairs. Antibody transfer to the litters was quantified and the offspring were challenged with RSV at different ages for analysis of protection against viral replication and lung inflammation. There was a strong correlation between RSV-neutralizing antibody (NA) titers in cotton rat mothers and their pups, which also correlated with protection of litters against virus challenge. Passive protection was short-lived and strongly reduced in animals at 4 weeks after birth. Protection of litters was significantly enhanced by inoculating mothers parenterally with live RSV and inversely correlated with the expression of lung cytokines and pathology. Importantly, vaccination and boosting of naïve mothers with the live RSV produced the highest levels of NAs. We conclude that maternal vaccination against RSV in the cotton rat can be used to define vaccine preparations that could improve preexistent immunity and induce subsequent transfer of efficient immunity to infants.

Effects of an invasive ant and native predators on cotton rat recruitment and survival

We used the imported red-fire ant (Solenopsis invicta; hereafter fire ant) and hispid cotton rat (Sigmodon hispidus) as model species to address the population-level effects of an invasive ant on a semiprecocial small mammal. We stocked cotton rats into 8 enclosures, implementing a 2-way factorial design with predator (ambient or excluded) and fire ant (ambient or reduced) treatments as factors. We trapped monthly from June 2012 to June 2013 and calculated monthly recruitment and survival. Rats in enclosures with ambient predators had a risk of mortality approximately 2 times greater than rats in enclosures with predators excluded. The risk of mortality was 3 and 4.5 times greater for female and male cotton rats, respectively, in enclosures with ambient fire ants and predators compared to enclosures with reduced fire ants and excluded predators. We found no effects on recruitment. Our results indicate that native predators had the greatest influence on cotton rat populations. Nevertheless, in the absence ...

Sa2017 Blocking Peripheral Serotonin Synthesis by Telotristat Etiprate Reduces the Severity of Both Chemical- and Infection-Induced Intestinal Inflammation

G A A b st ra ct s was recorded at termination. Blood was collected for determination of serum gastrin. The histological changes in the stomachs were examined. The presence of dysplasia and carcinoma on the anterior and posterior side of the stomachs were compared, and the oxyntic mucosal thickness and neuroendocrine (chromogranin A positive) cell density were calculated. Results: Ten of fifteen animals operated by anterior vagotomy and 11 of 16 sham-operated developed hypergastrinemia. Vagotomy did not affect intragastric pH or serum gastrin. There was no difference between innervated and denervated oxyntic mucosa in dysplasia and carcinoma development. However, vagotomy resulted in lower stomach weight in hypergastrinemic animals (2.8 ± 0.26 g vs. 3.7 ± 0.39 g, p=0.027) and reduced oxyntic mucosal thickness on the anterior side (0.83 ± 0.06 mm vs. 1.13 ± 0.1 mm, p ,0.01). Vagotomy also resulted in a reduction in volume density of chromogranin A positive cells in the oxyntic mucosa (12.1 ± 1.8 % vs. 18.8 ± 3.0 %, p=0.04). Conclusions: Unilateral truncal vagotomy reduced the trophic effects of hypergastrinemia on the ECL cell and oxyntic mucosa, but did not prevent gastric carcinogenesis in female Japanese cotton rats. The effects of vagotomy on gastric carcinogenesis in animal models are conflicting and further studies in patients should be done to clarify the clinically significant effects of vagotomy.

Sa2014 Unilateral Truncal Vagotomy Reduces Stomach Weight, Oxyntic Mucosal Thickness and Neuroendocrine Cell Density but Does Not Prevent Gastric Carcinoma Development in Hypergastrinemic Female Japanese Cotton Rats

Sa2014 Unilateral Truncal Vagotomy Reduces Stomach Weight, Oxyntic Mucosal Thickness and Neuroendocrine Cell Density but Does Not Prevent Gastric Carcinoma Development in Hypergastrinemic Female Japanese Cotton Rats

Sa2015 Signaling in Bile Acid-Induced DNA Damage in Barrett's Esophageal Adenocarcinoma Cells

G A A b st ra ct s was recorded at termination. Blood was collected for determination of serum gastrin. The histological changes in the stomachs were examined. The presence of dysplasia and carcinoma on the anterior and posterior side of the stomachs were compared, and the oxyntic mucosal thickness and neuroendocrine (chromogranin A positive) cell density were calculated. Results: Ten of fifteen animals operated by anterior vagotomy and 11 of 16 sham-operated developed hypergastrinemia. Vagotomy did not affect intragastric pH or serum gastrin. There was no difference between innervated and denervated oxyntic mucosa in dysplasia and carcinoma development. However, vagotomy resulted in lower stomach weight in hypergastrinemic animals (2.8 ± 0.26 g vs. 3.7 ± 0.39 g, p=0.027) and reduced oxyntic mucosal thickness on the anterior side (0.83 ± 0.06 mm vs. 1.13 ± 0.1 mm, p ,0.01). Vagotomy also resulted in a reduction in volume density of chromogranin A positive cells in the oxyntic mucosa (12.1 ± 1.8 % vs. 18.8 ± 3.0 %, p=0.04). Conclusions: Unilateral truncal vagotomy reduced the trophic effects of hypergastrinemia on the ECL cell and oxyntic mucosa, but did not prevent gastric carcinogenesis in female Japanese cotton rats. The effects of vagotomy on gastric carcinogenesis in animal models are conflicting and further studies in patients should be done to clarify the clinically significant effects of vagotomy.

The effects of unilateral truncal vagotomy on gastric carcinogenesis in hypergastrinemic Japanese female cotton rats

The stomach is innervated by the vagal nerve. Several studies have demonstrated that the vagal nerve has a trophic effect on the rat oxyntic mucosa and that the trophic effect of hypergastrinemia is dependent on intact vagal innervation. The effect of vagal denervation on gastric carcinogenesis has been examined in Mastomys natalensis and hypergastrinemic transgenic INS-GAS mice, with no effect of unilateral vagotomy in Mastomys but an anti-carcinogenic effect in INS-GAS mice.A proportion of female Japanese cotton rats develop spontaneous hypergastrinemia and ECL cell derived gastric carcinomas. In the current study we have examined the effects of unilateral anterior subdiaphragmatic vagotomy on gastric carcinogenesis. Female Japanese cotton rats were operated with unilateral anterior vagotomy or sham-operation at age 2months and were terminated at age 10months. Ten of fifteen animals operated by anterior vagotomy and 11 of 16 sham-operated developed hypergastrinemia. Vagotomy did not affect intragastric pH or serum gastrin. When comparing the anterior and posterior sides of the stomachs, vagotomy did not affect the occurrence of dysplasia or carcinoma development in the oxyntic mucosa. However, vagotomy resulted in lower stomach weight and reduced oxyntic mucosal thickness on the anterior side. Vagotomy also resulted in a reduction in volume density of chromogranin A positive cells in the oxyntic mucosa.In conclusion, vagotomy reduced the trophic effects of hypergastrinemia on the ECL cell and oxyntic mucosa, but did not prevent gastric carcinogenesis in female Japanese cotton rats. The effects of vagotomy on gastric carcinogenesis in animal models are conflicting and further studies in patients should be done to clarify the clinically significant effects of vagotomy.

Effect of antrectomy in hypergastrinaemic female Japanese cotton rats

Objective. Female Japanese cotton rats become hypoacidic and hypergastrinaemic from age 2 months and later develop gastric carcinomas in the oxyntic mucosa. Previous studies have demonstrated that carcinogenesis can be halted by a gastrin receptor antagonist and that carcinomas can be induced by a histamine-2 receptor antagonist or partial corpectomy, both of which induce hypergastrinaemia. The aim of the present study was to examine the effect of antrectomy in female cotton rats. Material and methods. The animals were either antrectomized (Group 1) or sham-operated (Group 2) 2 months after detection of hypergastrinaemia and terminated 4 months after operation. A third group was antrectomized at age 2 months while still normoacidic (Group 3) and terminated 6 months after operation. Results. Antrectomy after 2 months of hypergastrinaemia prevented the development of carcinoma compared with in sham-operated animals, whereas some of the animals that were antrectomized at 2 months of age also developed carcinomas. In Groups 1 and 2 as well as in animals developing carcinomas in Group 3, there was marked hyperplasia of neuroendocrine cells in the oxyntic mucosa expressing chromogranin A, vesicular monoamine transporter (VMAT)-2, ghrelin and somatostatin. Gastrin-positive cells were found adjacent to neoplastic areas in the oxyntic mucosa. Conclusions. The removal of antral gastrin by antrectomy halts carcinogenesis in cotton rats, but other mechanisms may also play a role.

Mechanisms of Habitat Selection by the Hispid Cotton Rat (Sigmodon hispidus)

The Texas coastal prairie is composed of habitat patches characterized by monocots, dicots, or a mixture of both plant types. Radiotelemetry revealed that reproductive female hispid cotton rats (Sigmodon hispidus) preferred mixed habitats and avoided dicot habitats, whereas males did not show a preference. Such habitat selection can be attained by shorter distances moved or increased turning (i.e., area-restricted search). Reproductive females, but not males, moved shorter distances in mixed habitats. However, turns relative to straight-ahead movements for females, but not males, were fewer in mixed habitats than in monocot or dicot habitats suggesting directed foraging rather than area-restricted search. To obtain necessary amounts of nutrients, especially carbohydrates, protein, phosphorus, and calcium, reproductive females ingest both monocots and dicots. Directed movement may facilitate foraging for dicots because these food items occur in clumps in mixed habitats. Because their nutritional needs are less than those of females, males do not exhibit the same patterns of habitat selection. Differential patch occupancy was not explained by overhead plant cover, but more bare ground in dicot habitats may explain avoidance of these habitat types because of increased predation risk.

Dedifferentiation of enterochromaffin‐like cells in gastric cancer of hypergastrinemic cotton rats

The role of enterochromaffin-like (ECL) cells in gastric carcinogenesis is not fully understood. Spontaneous tumours developing in hypergastrinemic female cotton rats have an adenocarcinoma phenotype, but numerous cells in the dysplastic mucosa as well as in the carcinomas are positive for neuroendocrine markers. In the present study of female cotton rats with 2 and 8 months' hypergastrinemia, the oxyntic mucosa of the stomach was examined histologically and immunolabelled for histidine decarboxylase (HDC) and pancreastatin, and hyperplastic and neoplastic ECL cells were evaluated by electron microscopy. These animals developed hyperplasia of the oxyntic mucosa in general and of the ECL cells in particular after 2 months and dysplasia and carcinomas after 8 months. The immunoreactivity of the ECL cells in the oxyntic mucosa was increased at 2 months and declined at 8 months. These histological changes were associated with progressive loss of secretory vesicles and granules in ECL cells. We suggest that ECL cells in hypergastrinemic cotton rats dedifferentiate with time and that the gastric carcinomas may develop from ECL cells.

Spontaneous enterochromaffin-like cell carcinomas in cotton rats (Sigmodon hispidus) are prevented by a somatostatin analogue.

Among inbred female cotton rats (Sigmodon hispidus) 25-50% of the animals develop spontaneous gastric carcinomas; the corresponding figure for male cotton rats is approximately 1%. Animals with carcinomas have hypergastrinaemia and gastric hypo-anacidity and the tumours are derived from enterochromaffin-like (ECL) cells. The mechanism behind the hypo-anacidity is unknown. Carcinomas are found in all female cotton rats with hypergastrinaemia lasting more than 4 months and this represents an excellent animal model for studying gastric carcinogenesis. In this study, the somatostatin analogue octreotide was given to female cotton rats to prevent carcinoma development caused by hypergastrinaemia. Twelve female cotton rats were given monthly injections of long-acting octreotide (5 mg i.m.) for 6 months. A control group of 20 animals was not given injections. Of the 20 control animals, 13 developed hypergastrinaemia and histologically invasive carcinomas or dysplasia. Of the 12 animals in the octreotide group, five developed hypergastrinaemia. None of these five animals developed histological cancer (P<0.05), whereas three had dysplasia. However, octreotide did not affect plasma gastrin concentration or antral gastrin mRNA abundance significantly. Dysplasia of the oxyntic mucosa in hypergastrinaemic animals was accompanied by a marked increase in chromogranin A-immunoreactive cells and cells positive for Sevier-Munger staining. The malignant tissue also contained groups of cells with Sevier-Munger staining. In conclusion, octreotide prevented ECL cell carcinomas in hypergastrinaemic cotton rats without lowering the gastrin concentration.

Hypergastrinaemia induced by partial corpectomy results in development of enterochromaffin‐like cell carcinoma in male Japanese cotton rats

Background: Among inbred female cotton rats (Sigmodon hispidus) 25%–50% of the animals develop spontaneous gastric carcinomas, whereas males have an incidence of less than 1%. The carcinomas are enterochromaffin‐like (ECL)‐cell derived. Animals with gastric carcinomas also have hypergastrinaemia and gastric hypoacidity, but the mechanism behind the hypoacidity is unknown. Carcinomas have been found in all female cotton rats with spontaneous hypergastrinaemia lasting more than 4 months, and a gastrin receptor antagonist prevents the development of carcinoma. The purpose of the present study was to investigate whether induced hypergastrinaemia in male cotton rats would also result in carcinomas. Methods: Hypergastrinaemia was induced by partial corpectomy of male cotton rats, aiming at removal of 80%–90% of the corpus. A control group was sham‐operated. Results: All partially corpectomized animals developed persistent hypergastrinaemia. Six months after the operation, 9 out of 13 partially corpectomized animals developed gastric cancer. In the dysplastic mucosa surrounding the tumours there was an increase in chromogranin A immunoreactive cells, where numerous cells also were stained using the Sevier‐Munger technique. Tumour tissue also contained cells that were chromogranin A positive and stained by Sevier‐Munger. Conclusions: ECL‐cell carcinomas can be induced in male cotton rats by partial corpectomy. This supports a previous statement that spontaneous carcinomas in female cotton rats are caused by gastric hypoacidity and hypergastrinaemia. In hypergastrinaemic animals, ECL‐cell carcinomas develop independently of gender within a relatively short period of time, and cotton rats therefore represent an interesting model for studying gastric carcinogenesis.

Spontaneous ECL cell carcinomas in cotton rats: natural course and prevention by a gastrin receptor antagonist.

In our inbred strain of cotton rats (Sigmodon hispidus) 50% of the females develop spontaneous ECL cell-derived tumors in the acid-producing part of the stomach due to hypergastrinemia secondary to gastric hypoacidity. Although the mechanism behind the hypoacidity is unknown, the female cotton rat is an excellent model for studying ECL cell-related tumorigenesis. In this study we wanted to explore the malignancy potential of these tumors and the ability of a gastrin receptor antagonist (YF476) to prevent their development. First, nine hypergastrinemic female cotton rats (10 months of age) were diagnosed by laparotomy as having gastric tumors. They were killed 6 months later. Second, 18 female cotton rats (2 months of age) were dosed monthly for 6 months with YF476 (500 micro mol/kg body wt) by s.c. injection, while 21 age-matched animals received vehicle. Samples from each stomach were collected for histology, immunohistochemistry and northern blot analysis. The gastric tumors harbored cells with immunohistochemical features of ECL cells. The tumors were found at times to invade and penetrate the stomach wall and to metastasize to perigastric sites. ECL-derived tumor cells were discovered in peritoneal fluid. At death only 1 out of 18 animals given YF476 displayed carcinomas (invasive growth), compared with 7 out of 21 in the vehicle dosed control group (P = 0.048). The spontaneous gastric tumors in cotton rats derived from ECL cells. The tumors were able to penetrate the stomach wall and to metastasize by intracavital seeding. Gastrin receptor blockade lowered the incidence of such tumors. We propose that the tumors are ECL cell carcinomas and that gastrin is the driving force behind the transformation from normal to malignant ECL cells.

Hypergastrinemia induced by partial corpectomy results in ECL-cell carcinoma in male cotton rats

Approximately 50 percent of females and one percent of males in a strain of Japanese cotton rats (Stgmodon hispidns) develop spontaneous enterochromaffm-like(ECL)-ceU derived gastric carcinomas and have hypergastrinemia secondary to gastric hypo/anacithty. The mechanism behind the hypo/anacidity is unknown. We have found carcinomas in all female cotton rats with spontaneous hypergastrinemia lasting more than four months. These animals represent an excellent model for studying ECL-cell carcinogenesis. The development of these tumors is prevented by a gastrin antagonist as well as by a somatostatin analogue. We have therefore previously argued that the carcinogenesis is due to hypergastrinemia. Whether induced hypergastrinemia would result in ECL-cell carcinomas cotton rats has not been examined. We therefore performed partial corpectomy, an operation that has resulted in persistent hypergastrinemia and ECDcell derived tumors in Sprague-Dowley rats more than two years postoperatively. Male cotton rats were chosen as they have the lowest incidence of spontaneous carcinomas. Male cotton rats were operated b)' ~n ia l corpectomy aiming at removal of 90% of the corpus. A control group was sham-operated. All animals were given B 12-injections monthly. Serum gastrin was measured every second month. At termination the stomach was examined histologically (haematoxylin and eosin) and immunohistochemically with an antibody against chromogranin A, a neuroendocrine cell marker. All partially corpectomized animals developed persistent hypergastrinemia and ECL-cell derived cancer after six months. Immunohistochemieal examination confirmed a neuroendocrine origin of the tumors. This study demonstrates that ECL-ceU carcinomas can be induced in male cotton rats in six months. The results support our previous statement that spontaneous tumors developing in cotton rats are caused by gastric hypoacidity and hypergastrinemia. Given persistent hypergastrinemia, ECL--cell carcinomas will develop in cotton rats independent of sex within a relatively short period of time.

Ecotoxicological Risks Associated with Land Treatment of Petrochemical Wastes. II. Effects on Hepatic Phase I and Phase II Detoxification Enzymes in Cotton Rats

The purpose of this study was to evaluate possible exposure and resultant hepatic effects of petrochemical waste on cotton rats (Sigmodon hispidus) living on landfarmed sites. Male and female cotton rats were collected in summer, fall, and winter from four landfarm sites and four ecologically similar reference sites. Hepatic methoxyresorufin O-deethylase (MROD) activity was significantly induced in male and female rats collected from landfarms compared to rats collected from reference sites. In contrast, changes in ethoxyresorufin O-deethylase (EROD) activity were inconsistent due to season, sex, and treatment variation. A significant decrease in EROD and MROD activity was found in cotton rats held for 48 h prior to sacrifice compared to rats euthanized on the day of capture. These results indicate that when using hepatic EROD and MROD activities as biochemical markers of exposure to aryl hydrocarbon receptor agonists, animals should be euthanized as quickly as possible after capture. The cotton rats collected from one landfarm unit exhibited a pattern of consistent elevation of EROD, MROD, and pentoxyresorufin O-deethylase (PROD) activity. This unit also had a pattern of elevated CYP1A2 protein expression determined by Western blotting. There were no consistent alterations from contaminant exposure on hepatic glutathione S-transferase (GST) activity, glutathione levels, or CYP1A1 protein. Hepatic EROD and MROD activities varied considerably between seasons and sex of rats. In conclusion, consistent induction of hepatic EROD and MROD activities in cotton rats was found in three out of four sampled landfarm sites compared to the rats collected from the reference sites, indicating exposure to contaminants--likely polyaromatic hydrocarbons.

Consequences of Diet Choice by a Small Generalist Herbivore

We examined the energy, nutrient, time, and habitat consequences of diet choice by a generalist herbivore, the hispid cotton rat (Sigmodon hispidus) on the Texas coastal prairie. Benefit–cost and linear programming models were developed and used to test several specific hypotheses about diet choice, foraging strategy, and habitat use by cotton rats. Within cotton rat habitat, there were significant differences among both seasons and habitat patches in the abundance and biomass of foods available. Monocot patches typically were higher in standing crops of energy and nutrients than were either dicot or mixed patches. Relative to available biomass and nutrients in dicot foods, this cotton rat habitat was both spatially and temporally heterogeneous and dynamic. Although the abundance of dicot foods in a habitat patch did influence costs of foraging time, time costs of cotton rats foraging for suitable foods did not decrease when standing crops of energy and nutrients in these habitats increased. Higher requirements for energy and nutrients needed for lactation by reproductive cotton rats resulted in higher foraging costs than for nonreproductive female rats. A mixed diet incorporating both monocot and dicot foods was nutritionally superior to either a monocot-only diet or a dicot-only diet. A diet of only monocots would meet minimum daily energy requirements and would not exceed either maximum daily digestive capacity or maximum daily foraging time, but it would not meet minimum daily requirements for protein and phosphorus during reproduction. Conversely, a diet of only dicots would meet nutrient requirements for reproduction but would exceed maximum daily foraging time. Mixing of monocot and dicot plant parts in the diet met both net energy and nutritional requirements, and increased foraging time, as compared to a diet of only monocots. Diets of cotton rats foraging to maximize net energy intake each season differed from the observed diets. Likewise, diets of cotton rats foraging to minimize total daily foraging time differed from the observed diets. Thus, we conclude that reproductive females of this generalist herbivore neither maximized their energy nor minimized their time, but rather, consumed a mixed diet to balance intake of requisite nutrients. Accordingly, a diet choice that included a mixture of monocot and dicot foods was most efficient when foraging occurred in a habitat having a mixture of monocot and dicot plants. Mixed patches provided higher energy and nutrient benefits to foraging cotton rats than did either monocot or dicot patches. Finally, we observed that reproductive female cotton rats concentrated their activities in mixed-patch habitats.

CONSEQUENCES OF DIET CHOICE BY A SMALL GENERALIST HERBIVORE

We examined the energy, nutrient, time, and habitat consequences of diet choice by a generalist herbivore, the hispid cotton rat (Sigmodon hispidus) on the Texas coastal prairie. Benefit-cost and linear programming models were developed and used to test several specific hypotheses about diet choice, foraging strategy, and habitat use by cotton rats. Within cotton rat habitat, there were significant differences among both seasons and habitat patches in the abundance and biomass of foods available. Monocot patches typically were higher in standing crops of energy and nutrients than were either dicot or mixed patches. Relative to available biomass and nutrients in dicot foods, this cotton rat habitat was both spatially and temporally heterogeneous and dynamic. Although the abun- dance of dicot foods in a habitat patch did influence costs of foraging time, time costs of cotton rats foraging for suitable foods did not decrease when standing crops of energy and nutrients in these habitats increased. Higher requirements for energy and nutrients needed for lactation by reproductive cotton rats resulted in higher foraging costs than for non- reproductive female rats. A mixed diet incorporating both monocot and dicot foods was nutritionally superior to either a monocot-only diet or a dicot-only diet. A diet of only monocots would meet minimum daily energy requirements and would not exceed either maximum daily digestive capacity or maximum daily foraging time, but it would not meet minimum daily requirements for protein and phosphorus during reproduction. Conversely, a diet of only dicots would meet nutrient requirements for reproduction but would exceed maximum daily foraging time. Mixing of monocot and dicot plant parts in the diet met both net energy and nutritional requirements, and increased foraging time, as compared to a diet of only monocots. Diets of cotton rats foraging to maximize net energy intake each season differed from the observed diets. Likewise, diets of cotton rats foraging to minimize total daily foraging time differed from the observed diets. Thus, we conclude that repro- ductive females of this generalist herbivore neither maximized their energy nor minimized their time, but rather, consumed a mixed diet to balance intake of requisite nutrients. Accordingly, a diet choice that included a mixture of monocot and dicot foods was most efficient when foraging occurred in a habitat having a mixture of monocot and dicot plants. Mixed patches provided higher energy and nutrient benefits to foraging cotton rats than did either monocot or dicot patches. Finally, we observed that reproductive female cotton rats concentrated their activities in mixed-patch habitats.