Life Span and Spontaneous Tumors Incidence of the Wistar Mishima (WM/MsNrs) Rat.

Fukuda, Satoshi; Iida, Haruzo

doi:10.1538/expanim.52.173

Cited by 11 publications

(7 citation statements)

References 21 publications

(23 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the literature, the incidences of spontaneous liver tumor are variable in different rat strains but are around 0.5–2% from 24–30‐month observation studies. ( 36–39 ) The rate of spontaneous GST‐A4‐positive foci in the present study is higher than the above values. This suggests that rats used in this study are sensitive not only to PP but also to spontaneous tumorigenesis.…”

Section: Discussioncontrasting

confidence: 69%

Glutathione S‐transferase A4 is a positive marker for rat hepatic foci induced by clofibrate and genotoxic carcinogens

et al. 2010

View full text Add to dashboard Cite

Peroxisome proliferators (PP), including clofibrate (CF), are nongenotoxic rodent carcinogens, and oxidative DNA damages are suggested as a causative event for carcinogenesis. Gene expression profiles differ between hepatic lesions induced by PP and genotoxic carcinogens. Our previous study revealed that expression of L-bifunctional enzyme (enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase, BE) was repressed in preneoplastic lesions induced by PP, whereas it was enhanced in the surrounding tissues. In the present study, we immunohistochemically examined expression of the specific glutathione S-transferase (GST) form, GST-A4, which detoxifies 4-hydroxy-alkenal, the end-product of lipid peroxides, and nuclear factor-erythroid 2-related factor 2 (Nrf2), a transcription factor for many genes encoding drug-metabolizing enzymes and defending enzymes against oxidative stress, during rat hepatocarcinogenesis induced by CF and genotoxic carcinogens. GST-A4 and Nrf2 were not expressed in BE-negative foci at 8 weeks of CF administration, but were expressed in the foci at 60 weeks. GST-A4-positive foci appeared at later stages than BEnegative foci, but its localization was coincidental with that of the latter foci. The areas of GST-A4-positive foci were larger than those of BE-negative foci without GST-A4 expression. Most GST-A4-positive foci were also positive for Nrf2. In rat livers induced by genotoxic carcinogens, GST-P-negative foci as well as GST-P-positive foci were demonstrated. GST-A4 and Nrf2 were expressed in GST-P-negative foci, whereas they were not expressed in most GST-P-positive foci. Thus, GST-A4-positive foci developed in rat livers by CF and genotoxic carcinogen administration, indicating that the enzyme is a positive marker for hepatic foci induced by these different carcinogens. (Cancer Sci 2010; 101: 1093-1098 P eroxisome proliferators (PP), including clofibrate (CF), induce hepatomegaly, proliferation of peroxisomes, and expression of several peroxisomal enzymes in rodent livers, such as acyl-CoA oxidase and L-bifunctional enzyme (BE), which participate in the b-oxidation of fatty acids and result in the production of hydrogen peroxide.(1-3) Prolonged administration of PP to rats is associated with the development of hepatic preneoplastic and neoplastic lesions.(4,5) As PP do not cause mutagenic effects in short-term in vitro assays, (6,7) administration of PP to rats for 60-100 weeks is required to evaluate their carcinogenic potential. PP include a broad spectrum of compounds of industrial, pharmaceutical, and agricultural importance, such as phthalate ester plasticizers, lipid-lowering drugs, and herbicides.(8) Thus, methods for early detection of the carcinogenic potential of PP are required. PP are non-genotoxic rodent carcinogens and their carcinogenic processes are suggested to differ from the processes of genotoxic carcinogens. (6,7) Gene expression profiles differ between hepatic lesions induced by PP and those by genotoxic agents.(9,10) The former lesions do not express GST-P, (11) a relia...

show abstract

Section: Discussioncontrasting

confidence: 69%

Glutathione S‐transferase A4 is a positive marker for rat hepatic foci induced by clofibrate and genotoxic carcinogens

et al. 2010

View full text Add to dashboard Cite

show abstract

“…Our results indicate that the ages at which total BMD decreases began were different: 15 months in the femur and tibia, 24 months in the humerus and 18 months in the first lumbar vertebra, respectively. We observed that the average life span of females of this strain was 813 ± 214 days (n=907), and mammary tumors began to appear after 18-24 months, with the final incidence being 20.1% [10]. Namely, the age when the BMD in long bones and first lumbar vertebra begins to decrease may overlap in time with or be close to the onset of tumors.…”

Section: Discussionmentioning

confidence: 87%

“…Our report regarding the life span and incidence of tumors in this strain is available to aid in our understanding of the changes in bones with age in rats as laboratory animals [10].…”

mentioning

confidence: 99%

Age-Related Changes in Bone Mineral Density, Cross-Sectional Area and the Strength of Long Bones in the Hind Limbs and First Lumbar Vertebra in Female Wistar Rats

Fukuda¹,

Iida²

2004

The Journal of Veterinary Medical Science

Self Cite

View full text Add to dashboard Cite

ABSTRACT. Age-related changes in bone mineral density (BMD) and cross-sectional area and bone strength index (SSI) of the femur, tibia, humerus, and first lumbar vertebra in female Wistar (WM/MsNrs) rats were examined by a quantitative computed tomography (pQCT) method. One hundred and sixteen virgin female Wistar (WM/MsNrs) rats aged 2-33 months were used. The data indicate that the to tal BMD values of metaphyses and diaphyses of long bones increased until 12 months, then decreased to a varying degree depending on the bone after 15-24 months, but the values of cortical and trabecular BMD with age were not always similar to the total BMD value. Nevetheless, the values for cross-sectional area and SSI in the long bones increased regardless of the total BMD decrease with a ge, indicating that this increase might have been due to a characteristic of the modeling pattern in rats. The total and cortical BMD values in the first lumbar vertebra decreased after 18 months, and SSI did after 15 months. The data obtained in this study were compared with those obtained from males in a previous study. In conclusion, it was indicated that in this strain the rats over 12 months with the highest total BMD values in the femur and tibia, and before the onset of various tumors, are useful as a model animal for osteoporosis experiments and observation of senile bone change. KEY WORDS: bone mineral density, cross-sectional area, female Wistar rat (WM/MsNrs), pQCT, strength strain index.J. Vet. Med. Sci. 66 (7): [755][756][757][758][759][760] 2004 We have previously reported the age-related changes in bone mineral density (BMD), cross-sectional area, and strength strain index (SSI), an indicator of bone fragility, in male rats [17], as rats are widely used for experiments regarding bone disease and for pharmacological tests. Female rats are more frequently used than males, for example, as a model of postmenopausal osteoporosis after ovariectomy treatment. Nevertheless, the differences between rats and humans in bone metabolic and morphologic characteristics have been contested [2,7,8,18,25,34]. Furthermore, although many studies on bones in the rat have carried out, the data have varied because of differences in the bones observed and the measurement methods [3,9,11,13,16,22,27,32,33].We consider it important to clarify the age-related changes in bones throughout the life span of rats to determine whether it is worthwhile to use rats in studies related to bones. Our report regarding the life span and incidence of tumors in this strain is available to aid in our understanding of the changes in bones with age in rats as laboratory animals [10].The measurement of BMD, cross-sectional area, and SSI in the present study was done by the QCT method because this method has merits with regard to simultaneously measuring BMD and morphologic features by separating trabecular and cortical bones, and because it can be carried out in live rats, the same as in clinical use for humans, as described previously [17].The purpose of the present stud...

show abstract

“…The environment was maintained at 22°C on a 12‐h light/12‐h dark cycle. The 5‐month‐old (young‐adult) rats have ended their main growth spurt and are mature, whereas the 25‐month‐old rats are considered old; the Wistar rat has a median lifespan of 21.5 months (Harlan Laboratories, Indianapolis, Indiana) and a mean life expectancy of around 24 months 29, 30. Rats were randomly assigned to groups in which the left gastrocnemius muscle was subjected to 1, 2, or 4 weeks of denervation, whereas the right gastrocnemius muscle served as an internal control, as described previously 9.…”

Section: Methodsmentioning

confidence: 99%

Time‐course of changes in the myonuclear domain during denervation in young‐adult and old rat gastrocnemius muscle

et al. 2011

View full text Add to dashboard Cite

If myonuclear loss initiates muscle wasting, it should precede the loss of muscle mass. As aging affects muscle plasticity, the time-course of muscle atrophy during disuse may differ between young and old animals. To investigate this, gastrocnemius muscles of 5-and 25-month-old rats were exposed to 1, 2, or 4 weeks of denervation, whereas the contralateral gastrocnemius muscles served as controls. Muscle fibers of each type responded similarly to 4 weeks of denervation. For both ages most of the atrophy (36%; P < 0.001) occurred in the first 2 weeks. In young-adult muscles, the myonuclear number remained constant, but in old muscles it decreased to below control level after 4 weeks of denervation (P < 0.05). Despite this differential response, myonuclear domain size decreased similarly at both ages (P < 0.001). In both young-adult and old rats, denervation-induced atrophy was not preceded by a loss of myonuclei.

show abstract

Life Span and Spontaneous Tumors Incidence of the Wistar Mishima (WM/MsNrs) Rat.

Cited by 11 publications

References 21 publications

Glutathione S‐transferase A4 is a positive marker for rat hepatic foci induced by clofibrate and genotoxic carcinogens

Glutathione S‐transferase A4 is a positive marker for rat hepatic foci induced by clofibrate and genotoxic carcinogens

Age-Related Changes in Bone Mineral Density, Cross-Sectional Area and the Strength of Long Bones in the Hind Limbs and First Lumbar Vertebra in Female Wistar Rats

Time‐course of changes in the myonuclear domain during denervation in young‐adult and old rat gastrocnemius muscle

Contact Info

Product

Resources

About