Maternal behavior in F344/N and LEW/N rats. Effects on carrageenan-induced inflammatory reactivity and body weight

Inbred Fischer (F344/N) and Lewis (LEW/N) rats differ on a myriad of behavioral and physiological endpoints, such as inflammatory, startle and drug responsivity. These differences point to underlying genetic differences between the strains. However, genetic models of hypertension have shown the importance of the maternal environment in the development of high blood pressure, suggesting that maternal influences might also play a role in adult phenotypes of the LEW/N and F344/N strains. This was tested in the present series of experiments in which the effects of crossfostering on carrageenan-induced inflammation and on body weight were examined in the two strains. Following the demonstration that the two strains differed in maternal behavior (Experiment 1), which was independent of the pup being reared (Experiment 2), crossfostered and in-fostered pups from the LEW/N and F344/N strains were injected with carrageenan (at 60 days of age) and subsequently assessed for the accumulation of exudate in response to the injection. Body weights were also monitored from birth through 60 days of age. Although crossfostering affected body weight of the two strains, specifically, reducing weights in LEW/N pups reared by F344/N dams and increasing weights of F344/N pups reared by LEW/N dams, crossfostering did not affect inflammatory reactivity to carrageenan. Specifically, LEW/N pups had a greater level of exudate than F344/N pups, independent of the conditions under which they were reared, suggesting that differences in the inflammatory response between these two strains are under a high degree of genetic control. These results were discussed in terms of genetic factors mediating the early form of immune reactivity induced by carrageenan.     

Variable severity and Ia antigen expression in streptococcal-cell-wall-induced hepatic granulomas in rats

We have previously reported that a single intraperitoneal injection of an aqueous suspension of group A streptococcal cell wall (SCW) fragments induces extensive hepatic granulomas in LEW/N female rats, but not in F344/N female rats. To further understand the mechanisms underlying these differences, we compared granuloma development and class II major histocompatibility complex antigen (Ia) expression in histocompatible LEW/N, F344/N, and CAR/N female rats in response to SCW fragments of four different average molecular sizes. In LEW/N female rats, the smallest fragments (less than 5 megadaltons) induced the most severe hepatic inflammatory disease, with development of widespread granulomas composed of macrophages, lymphocytes, and a peripheral rim of fibroblasts. The largest fragments (greater than 500 megadaltons) induced equivocal disease. Fragments of intermediate size induced granulomas of intermediate severity. The extent of granuloma development, the intensity of Ia antigen expression, and the amount of SCW antigen deposited in the liver qualitatively paralleled each other. In contrast, injection of the most granulomagenic SCW fragments into F344/N and CAR/N rats did not induce granulomas. Although these rat strains are histocompatible with the LEW/N (i.e., RTL.1) strain, hepatic Ia antigen expression in these strains was not increased significantly above basal levels. The amount of SCW antigen in the livers of the resistant rat strains appeared similar to the amount in the susceptible LEW/N strain. These data indicate that granuloma development is dependent on the size of the SCW fragment and host genetic background and that Ia expression directly parallels the severity of the hepatic disease. In addition, the data suggest that non-major histocompatibility complex genetic loci play a major role in regulating the development of the hepatic disease.     

Effects of cross-fostering on cocaine-induced conditioned taste aversions in Fischer and Lewis rats

The systematic comparison between Fischer and Lewis rats is a popular animal model of genetic factors in drug abuse. Although genetic and environmental factors interact to affect drug abuse in humans, analogous effects have not yet been reported within the Fischer-Lewis model. In order to assess the contributions and interaction of genotype and early maternal environment on responses to a drug of abuse, the present study employed a cross-fostering design, where male and female Fischer and Lewis pups were reared by unrelated dams of their own strain (in-fostered) or of the other strain (cross-fostered). As adults, rats from both strains were tested for their ability to acquire a conditioned taste aversion to a novel saccharin solution that had been repeatedly paired with an injection of cocaine (32 mg/kg, subcutaneous). In-fostered Fischer females acquired significantly weaker aversions than in-fostered Lewis females across the multiple saccharin-cocaine pairings. However, cross-fostered Fischer females exhibited aversions that were not only significantly stronger than their in-fostered Fischer counterparts, but identical to all groups of the Lewis genotype. No strain differences or cross-fostering effects were observed in the males. The data with the female subjects cannot be accounted for simply by the genetic strain of the subjects and demonstrate a clear gene-environment interaction effect on responses to the aversive effects of cocaine in Fischer and Lewis rats. Implications for studying maternal behavior as a source of epigenetic modulation of drug abuse vulnerability were discussed.     

Serum antibody and cellular responses in LEW and F344 rats after immunization with Mycoplasma pulmonis antigens

Mycoplasma pulmonis causes a chronic respiratory disease in rats which is more severe in LEW than in F344 rats. This study compared the ability of each of these rat strains to produce specific immune responses to M. pulmonis antigens. By an enzyme-linked immunosorbent assay, LEW rats were found to produce approximately 10 times lower levels of specific immunoglobulin G (IgG) after immunization with M. pulmonis antigens than F344 rats, while no significant difference was found in the levels of IgM. The difference in IgG levels was due to much greater levels of specific IgG2b (about 50 times) in F344 rats; no differences were found in other subclasses. Nonimmune LEW rats were found to have as much total IgG2b in their sera as unimmunized F344 rats by a single radial immunodiffusion test; thus, the difference was not due to the inability of LEW rats to produce IgG2b. In contrast to the antibody response to M. pulmonis antigens, anti-keyhole limpet hemocyanin IgG responses in LEW and F344 rats were similar, but F344 rats produced significantly more (about 21 times) IgG2b than was found in M. pulmonis responses. Antisera from F344 rats recognized several additional M. pulmonis antigens than antisera from LEW rats; however, this could not explain the differences in the level of IgG2b in LEW and F344 rats. In vitro stimulation of splenic lymphocytes with M. pulmonis antigens from immunized F344 rats produced much greater proliferative responses than in LEW and nonimmune F344 cells. Thus, the susceptible rat strain LEW produced lower cellular and humoral immune responses to M. pulmonis antigens than the resistant rat strain F344 after immunization.     

Experimental allergic encephalomyelitis and corticosterone studies in resistant and susceptible rat strains

In an effort to understand the role of endogenous corticosterone production on the induction of experimental allergic encephalomyelitis (EAE) in rats, experiments in our study were performed using inbred rat strains that differ in basal corticosterone levels. Levels of corticosterone in serum samples were determined for LEW, WF, LER, and PVG rats, all of which had significantly lower corticosterone levels than BN or F344 rats. However, despite the twofold interstrain differences in basal concentrations, all animals tested showed considerable increases in corticosterone levels after being stressed by anesthesia. A series of determinations of steroid levels was made for LEW and BN rats during the postinflammatory periods of EAE induction; as expected, BN rats (EAE resistant) showed no change from their high basal levels, whereas LEW (EAE susceptible) showed consistent and long-lasting twofold increases in their circulating levels of corticosterone during the inflammatory process. Because the high corticosterone phenotype may be causally related to EAE resistance, [(BN x LEW) x BN]F1 backcross rats were tested for the possible coinheritance of the high corticosterone phenotype and EAE resistance. Contrary to the expectation of genetic linkage, our results demonstrate no correlation between the two genetic traits in this rat strain combination.     

Cutaneous inflammatory reactions to group A streptococcal cell wall fragments in Fisher and Lewis inbred rats.

Systemic administration of an aqueous suspension of group A streptococcal cell wall fragments induces severe, chronic erosive polyarthritis in LEW/N female rats, but rarely in F344/N female rats. In the present study, we attempted to exclude unresponsiveness to the cell walls as a mechanism for arthritis resistance in F344/N females. Cutaneous inflammatory reactions were assessed in both strains at various time points after direct injection of cell wall fragments of three different average molecular weights. Fragments of all sizes induced an acute inflammatory reaction, with infiltration of polymorphonuclear leukocytes and a few mononuclear cells. Small fragments (approximately 5 megadaltons) induced a transient response which resolved by day 14. Large fragments (approximately 500 megadaltons) induced severe inflammation characterized by prominent mononuclear leukocyte infiltration, whereas the intermediate-sized fragments (approximately 50 megadaltons) induced inflammation of intermediate intensity and duration. The intensity and severity of the lesions paralleled the persistence of cell wall antigens at the site of deposition. F344/N female rats responded acutely to the cell walls, with an intensity equal to or greater than that of LEW/N female rats, but the lesions tended to resolve more rapidly. These findings indicate that severity and chronicity of streptococcal cell wall-induced inflammation are dependent on the size of the fragment and provide evidence that arthritis resistance in F344/N female rats does not result from a completely unresponsive state to the proinflammatory effects of the cell walls.     

Regulation of resistance against adjuvant arthritis in the Fisher rat.

Inbred female Lewis (LEW/N) rats develop a severe chronic arthritis in the adjuvant arthritis (AA) model, histocompatible Fisher (F344/N) rats are resistant and germ-free Fishers (GF F344) are again susceptible. In this study we show that the F344 rat can become susceptible to AA, using Mycobacterium tuberculosis (M.tb.) in the powerful adjuvant paraffin oil, instead of mineral oil (Freund's incomplete adjuvant (FIA)). This indicates that the F344 rat does not lack T effector cells. To examine further mechanisms responsible for suppression, we determined the level of plasma corticosterone in response to IL-1 alpha in Lewis, F344 and GF F344 rats. IL-1 alpha induced only low amounts of corticosterone in Lewis rats, but high amounts in both F344 and GF F344 rats. The GF F344 rats are susceptible to AA, but the severity of the disease is reduced compared with Lewis rats. This indicates that corticosterone may be an important mechanism to suppress disease development, but not the only mechanism. In addition we investigated whether T suppressor cells play a role in the resistance of the F344 strain. This was performed by pretreating the animals with the immunomodulating drugs cyclophosphamide (Cy) and cyclosporin A (CsA). We were unable to make the F344 rat susceptible to AA, indicating that active suppression does not play a role in the induction phase of arthritis. This finding is confirmed in adoptive transfer experiments of AA from Lewis to F344 rats. Our data suggest the lack of a strong pre-existing suppression in the F344 rats, and indicate that suppression is generated upon bacterial challenge. Whether suppression is overruled probably depends on the power of adjuvants used and potential control by corticosteroids.     

Corticosterone increases depression-like behavior, with some effects on predator odor-induced defensive behavior, in male and female rats

This experiment examined the effect of repeated corticosterone injections on anxiety and depression-like behavior in male and female rats. Rats received either corticosterone or vehicle injections for 21 consecutive days prior to behavioral testing in the forced swim, open-field, and predator odor tests. The corticosterone injections significantly increased depression-like behavior in the forced swim test in both male and female rats but had no significant effect on anxiety in the open-field test. In the predator odor test, the corticosterone injections significantly increased a subset of defensive behaviors in the male rats. These results suggest that repeated exposure to corticosterone increases depression-like behavior, with some effects on anxiety, and that male rats may be more affected than female rats by this manipulation.     

Serum antibody does not account for differences in the severity of chronic respiratory disease caused by Mycoplasma pulmonis in LEW and F344 rats

Chronic respiratory disease in rats, resulting from Mycoplasma pulmonis infection, is useful in the study of the immunological mechanisms in similar inflammatory diseases and provides a unique opportunity to study the interactions between systemic and mucosal immune systems in a naturally occurring infection. The present study examined the serum antibody responses to M. pulmonis in strains of rats which differ in disease progression and severity; LEW rats developed more severe disease than did F344 rats. Serum antibody responses were evaluated as to their levels, isotypes, and antigens recognized. Infected LEW rats produced greater or equal levels of the major classes of serum antibody to M. pulmonis than did infected F344 rats, suggesting that development of serum antibody responses alone does not resolve lesions and is not responsible for the difference in disease severity found in LEW and F344 rats. Although LEW rats produced higher responses in all subclasses of immunoglobulin G (IgG), the specific IgG response of LEW rats was composed predominately of IgG1 and IgG2a subclasses, while IgG2b was the major component of the IgG response in F344 rats. Finally, LEW rats responded more quickly to M. pulmonis antigens than did F344 rats, and there was no difference in the antigens eventually recognized by each strain, confirming previous work which suggested that LEW rats do not exhibit an unresponsiveness to a specific antigen(s) of M. pulmonis.     

Cross-fostering Effects on Weight,Exploratory Activity,Acoustic Startle Reflex and Corticosterone Stress Response in Norway Gray Rats Selected for Elimination and for Enhancement of Aggressiveness Towards Human

Two rat lines, one tame, the other aggressive, differing by many behavioral features and stress reactivity were developed by long-term selection of wild gray rats for elimination and enhancement of aggressiveness towards humans. The aim of this work was to study the role of the maternal environment in the expression of these differences between the two rat lines using the cross-fostering paradigm. Fostering of tame rats of both sexes by aggressive mothers and aggressive females by tame mothers was without effect on behavior score towards humans, but the cross-fostered aggressive males had a small, yet significant, increase in aggressiveness score. Cross-fostering revealed that exploratory behavior in the hole-board test and the acoustic startle amplitude were weakly affected by maternal interactions, although there was an effect on body weight and on the stress corticosterone response. Body weight was decreased in tame males fostered by aggressive mothers only and it was increased in cross-fostered aggressive rats of both sexes. Fostering of tame males and females by an aggressive mother enhanced almost twofold the corticosterone response immediately after stress, while fostering of aggressive ratlings of both sexes by a tame mother was without effect. The current results demonstrated that the maternal postnatal environment had no substantial effect on the behavioral responses of both tame and aggressive rats, but it possibly contributed to the development of the corticosterone response to restraint stress in the tame, and not the aggressive rats, i.e. these effects of cross-fostering were dependent on ratling genotype. Edited by Tamara Phillips.     

Dark Agouti and Fischer 344 rats: differential behavioral responses to morphine and biochemical differences in the ventral tegmental area.

We sought to identify behavioral and biochemical differences between Dark Agouti and Fischer 344 inbred rat strains to assess whether they could serve as a model of genetically determined differences in sensitivity to drugs of abuse. We compared the strains for the following traits: morphine-induced locomotor activity and sensitization; circadian variation in plasma levels of corticosterone, a hormone reported to affect sensitivity to drugs of abuse; and several biochemical parameters in the ventral tegmental area and nucleus accumbens, brain regions implicated in the locomotor activating and reinforcing actions of drugs of abuse. Fischer 344 rats exhibited greater initial locomotor responses to morphine but, unlike Dark Agouti rats, did not develop sensitization to a second morphine exposure. Fischer 344 rats displayed a marked rise in basal plasma corticosterone levels in the late light phase and early dark phase, whereas Dark Agouti rats showed no significant circadian variation in corticosterone levels. Relative to drug-naive Fischer 344 rats, drug-naive Dark Agouti rats showed higher levels of tyrosine hydroxylase and glial fibrillary acidic protein, and lower levels of neurofilament proteins, in the ventral tegmental area. In contrast, no strain differences were found in levels of tyrosine hydroxylase, specific G protein subunits or protein kinase A in the nucleus accumbens. Together, these results demonstrate that Dark Agouti rats and Fischer 344 rats exhibit differences in specific behavioral, endocrine and biochemical parameters related to sensitivity to drugs of abuse.     

Rat strains differ in susceptibility to Ureaplasma parvum-induced urinary tract infection and struvite stone formation

Individuals with struvite uroliths are susceptible to recurrent urinary tract infections (UTI), sepsis, and renal disease. Unfortunately, little is known about the host-specific factors that predispose to this disease. In order to develop a rodent model that can address this problem, we inoculated female Fischer 344 (F344), Lewis (LEW), Sprague-Dawley (SD), and Wistar (WIS) rats with a host-adapted strain of Ureaplasma parvum. Animals were necropsied at 2 weeks postinoculation; 100% of F344, 42% of SD, 10% of LEW, and 10% of WIS rats remained infected. Severe bladder lesions and struvite calculi were seen in 64% of F344 rats; in other rat strains, bladder lesions were mild or absent. F344 rats with struvite uroliths had the highest urinary levels of proinflammatory cytokines, such as GRO/KC, interleukin-1alpha (IL-1alpha), and IL-1beta. F344 rats without struvite stones at necropsy had milder bladder lesions and significantly lower urinary levels of proinflammatory cytokines but a more prominent inflammatory response than did other rat strains. Based on our results, struvite stone formation is linked to a robust inflammatory response that does not resolve UTI but instead promotes damage to surrounding tissues.     

Differences between inbred rat strains in the alteration of adrenal catecholamine synthesizing enzyme activities after immobilization stress.

The effect of repeated immobilization on adrenal tyrosine hydroxylase, dopamine-beta-hydroxylase and phenylethanolamine N-methyltransferase activities was studied in male rats of several inbred strains. The activities of these enzymes increased in the adrenals of each strain, although there were quantitative differences between strains in the magnitude of the increases observed. The prerequisites of the response of adrenal enzymes to immobilization stress were studied in detail in two inbred strains (LEW and F344) using both surgical and pharmacological procedures. Surgical denervation of the adrenal gland does not affect the increases in enzyme activity observed in LEW male rats; hypophysectomy, however, results in the abolition of the changes in adrenal enzyme activity produced by immobilization. Conversely, adrenal denervation prevents the increase in activity of all three enzymes and hypophysectomy does not prevent the increased enzyme activities resulting from repeated immobilization in the F344 strain.These results suggest that distinct neuronal and pituitary-dependent mechanisms are responsible for increasing the activities of the enzymes of catecholamine synthesis in response to immobilization stress in the adrenal glands of these two inbred rat strains.     

Copulatory behavior, reproduction, and sperm competition in two strains of male rats.

Long-Evans males fathered 72% of the offspring when one Long-Evans and one F344 male mated repeatedly with the same female throughout her estrus. When each male was restricted to one ejaculation and the second male was allowed to begin mating immediately following the first male's ejaculation, the second male left more offspring in each strain. However, the proportion was significantly greater for Long-Evans males. In contrast, there were no strain differences in either number of pregnancies or litter size in noncompetitive matings limited to two ejaculations, the minimal number required to induce pregnancy. The only consistent behavioral differences were the greater number of intromissions performed with shorter latencies by F344 males, differences that cannot readily be used to explain their reduced success. It was hypothesized that the two strains may differ in the adequacy of penile reflexes used to form, set, or dislodge sperm plugs.     

Genetic influences on behavioral and neuroendocrine responses to predator-odor stress in rats

The exposure of animals to a variety of stressful events can induce behavioral and physiological responses, which can be modulated by anxiety levels. It is well recognized that genetic factors play a substantial role in both anxiety and stress reactivity. The present study examined the effect of exposure to 2,4,5-trimethylthiazoline (TMT), a component of fox feces, on nociception and corticosterone levels in Lewis (LEW) and Spontaneously Hypertensive (SHR) inbred rat strains (which display genetic differences in anxiety models such as the elevated plus-maze and open-field). The influence of two quantitative trait loci (QTL), named Ofil1 and Ofil2, which are known to affect emotionality in LEW versus SHR intercrosses on the responses to TMT was also investigated. LEW and SHR rats of both sexes displayed similar levels of behavioral and neuroendocrine responses after TMT exposure. As expected, TMT odor stress produced analgesia and enhanced corticosterone levels. Ofil1 on chromosome 4 affected stress-induced analgesia in males only. Ofil2 on chromosome 7 had no effect. The results suggest that behaviors measured in classical models of generalized anxiety and reactivity to stress produced by predator odors can be genetically dissociated. Finding a locus with an effect on the behavioral responses to stress represents the starting point in the search for genes responsible for stress-related traits.     

Development of the vasculature of the pars distalis in a tumor-susceptible strain of rat (Fischer 344) differs from vascular development in a non-tumor-susceptible strain (Lewis)

The development of the vasculature of the pars distalis of two strains of rat, Fischer 344 (F344) and Lewis (LEW), was followed in 16-day (16d) and 20-day (20d) fetuses, and in 1-day (1d), 5d, 20d, 50d, and 6-month-old females. No differences in the two strains were apparent in 16d fetuses; and the capillaries that were present were immature, i.e., tall, non-fenestrated endothelial cells, and were surrounded by poorly delineated pericapillary spaces. Immature capillaries also were predominant in 20d fetuses of both strains. Agranular folliculo-stellate cells were identifiable, projecting endfeet to the parenchymal basal lamina in 20d F344 fetuses, but not in LEW fetuses. Postnatally, the capillaries of LEW rats became progressively more thin-walled and fenestrated, and were surrounded by a pericapillary space that was well delimited by basal laminae at 20d. In 50d and 6-month LEW rats, capillaries were intact and surrounded by well-defined pericapillary spaces. By comparison in F344 rats, the capillaries remained more immature even in 50d rats and older. In addition, in F344 rats focal disruptions in endothelial cells and disruptions in parenchymal and capillary basal laminae were present in all postnatal stages, and a dramatic accumulation of plasma was evident within the pericapillary spaces at 20d. Endfeet processes of folliculo-stellate cells were abundant at the parenchymal basal lamina of 1d and 5d F344 neonates, but only rarely were identified in LEW neonates. Some activation of folliculo-stellate cells, i.e., increased numbers of lysosomes and dilated endoplasmic reticulum, was present in 50d F344 rats. Connective-tissue cells within the pericapillary space also were numerous and activated in F344 rats. Discrete gaps in the parenchymal basal lamina were evident subjacent to the folliculo-stellate cell endfeet in F344 rats but not in LEW rats. The vascular bed of F344 rats differs in its development from that of LEW rats. Characteristic of the F344 strain is a persistence of more immature capillaries, an inherent vascular fragility, and an activated state of folliculo-stellate cells.     

Murine respiratory mycoplasmosis in F344 and LEW rats: evolution of lesions and lung lymphoid cell populations.

By comparison of two strains, LEW and F344, which are known to differ in susceptibility to Mycoplasma pulmonis respiratory disease, it was shown that differences in lesion severity and progression were associated with changes in lung lymphocyte populations. Lung lesions in LEW rats developed earlier after infection, became more severe, and were characterized by continued proliferation of all classes of lymphoid cells, T lymphocytes, B lymphocytes, and plasma cells, throughout the 120-day observation period. In contrast, lymphoid proliferation in F344 rats reached a plateau at 28 days and was restricted to an increase in T lymphocytes, immunoglobulin A (IgA)-bearing B lymphocytes, and IgA and IgG plasma cells. Although approximately 10 times as many IgG B cells and 4 times as many IgG plasma cells were found in infected LEW rats as compared with F344 rats, the specific anti-M. pulmonis IgG response in the two strains was roughly parallel. The same relationships held true, although to a lesser extent, for specific IgA antibody responses and cellular responses. Whereas lung lesions showed a tendency to resolve in F344 rats by 120 days, severe lesions persisted in LEW rats. The disparity between the cellular response and specific antibody response, the seemingly uncontrolled lymphocyte proliferation in LEW rats, and the mitogenic potential of M. pulmonis suggest that differences between LEW and F344 rats in lung lesion severity and progression are related to differences in the degree of nonspecific lymphocyte activation in the two strains, an imbalance in regulation of lymphocyte proliferation in LEW rats, or both.     

Stress ulcer susceptibility and depression in Wistar Kyoto (WKY) rats

In a series of studies, Wistar Kyoto (WKY) normotensive rats were more susceptible to water-restraint-induced stress ulcer as compared to spontaneously hypertensive rats (SHR) Fisher-344 (F344) and Wistar rats. In these same studies, WKY rats were also deficient in several behavioral tasks. The four strains were observed in the open-field test of emotionality and WKYs were judged more emotional. In a study on "learned helplessness" WKYs were more deficient in the acquisition of a shuttlebox escape response following unavoidable shock the day before. The prevalence of freezing behavior in the shuttlebox task and the low ambulation scores in the open-field test suggested depressive behavior as a WKY behavior characteristic. WKY rats were judged more depressed in the Porsolt forced-swim test as compared to the other strains. A possible depression-ulcer relationship may exist in WKY rats. This strain may represent a good model for studying possible relationships between depression and stress-induced disease.     

Behavioral reactivity in spontaneously hypertensive rats

Spontaneously hypertensive rats of the Okamoto strain (SHR) were compared with inbred normotensive rats of the Wistar-Kyoto strain (WKY) and with normally bred Wistar rats (NT) in tests on the audiogenic immobility reaction (freezing), open-field behavior in a dark and an enlightened arena respectively, auditory startle response and male sexual behavior. Compared to the WKYs the SHRs showed increased locomotion and rearing in the open-field situations, reduced startle response and shortened immobility reaction. The SHRs differed in the same way from the NT rats with the exception for motor activity in the dark arena, where no differences were observed. The WKY rats showed less motor activity than the NT animals. Both SH and WKY rats showed shorter latency time for ejaculation than the NT rats. The characteristics of the behavior patterns displayed by the SH rats were interpreted as indicating a reduced propensity for fear reactions in this strain of rats compared to the WKY and NT strains used in the present study.     

INTESTINAL METAPLASIA INDUCED BY X-IRRADIATION IN DIFFERENT STRAINS OF RATS

Attempts were made to examine strain differences in the susceptibility of rats to intestinal metaplasia induced by X-irradiation. The gastric regions of 4 inbred male rats (SHR, F344, WKY, and LEW strains) in 5-week-old and 2 random bred male rats (SD, and WIS strains) were irradiated with a total dose of 20 Gy X-ray given in two equal fractions separated by three days. Upon sacrifice at 6 months after the last irradiation, the number of intestinal metaplastic crypts with positive reaction to alkaline phosphatase (ALP) appeared highest in the SHR and lowest in the WIS rats. Morphologically, the number of crypts with intestinal metaplasia in whole glandular stomachs of SHR, WIS, F344, and SD rats were higher than those in WKY and LEW rats. In the pyloric gland, it was highest in WIS rats, while in the fundic gland it was highest in SHR rats. The results show that the appearance and location of intestinal metaplasia by X-irradiation are greatly influenced by the strain of the rat. ACTA PATHOL. JPN. 35: 841–847, 1985.