The induction of cytochrome P-450 by isosafrole and related methylenedioxyphenyl compounds

Using sucrose gradients, the Ah receptor and a 3-4S binding peak were measured in hepatic cytosol from Dub: ICR, C57BL/6, and DBA/2 male mice. Isosafrole, piperonyl butoxide, and 5-t-butyl-1,3-benzodioxole were unable to displace 2,3,7,8-tetrachlorodibenzo-p-dioxin or 3-methylcholanthrene from either the Ah receptor or the 3-4S binding peak, in vitro. In in vivo experiments, treatment of C57BL/6 mice with 3-methylcholanthrene caused a 4-fold reduction in Ah receptor binding 2 h after i.p. injection; whereas, isosafrole caused a 2-fold enhancement of the Ah receptor after 24 h. This increase in the Ah receptor binding following isosafrole treatment may be due to induction. 3-Methylcholanthrene treatment of C57BL/6 mice also caused a 3-fold reduction in the 3-4S binding peak 2 h after i.p. injection; isosafrole treatment had little or no effect on the 3-4S peak in C57BL/6 or DBA/2 mice. Both in vivo and in vitro data appear to demonstrate that there is no direct role for the Ah receptor or the 3-4S protein in the regulation of cytochrome P-450 by methylenedioxyphenyl compounds. Using Sephadex G-100 chromatography, a cytosolic protein fraction was obtained from C57BL/6 and Dub:ICR mice which was previously implicated by others as a carrier in the metabolism of benzo[a]pyrene (B[a]P). This fraction was applied to sucrose gradients and sedimented in the 3-4S region. Hence it appears that the 3-4S binding peak may be the carrier described by these workers.     

Experimental Toxoplasma gondii infection in mice: the role of the fifth component of complement.

Experiments performed to determine the influence of the C5 component of complement in experimental Toxoplasma infection revealed that mice deficient in C5 had reduced mortality due to acute toxoplasmosis. Similar results were noted when inbred congenic mice of known complement type, as well as random-bred mice selected for complement type, were used. In both, mice with high complement activity were less resistant to Toxoplasma than were mice deficient in C5. However, many factors must interact in susceptibility to infection with T. gondii. Thus, lower resistance to Toxoplasma was noted in C5-deficient DBA/2J mice, whereas a high degree of resistance was noted in DBA/1J mice, which are not related to DBA/2J mice and which possess a normal sequence of complement. This accentuates the importance of using both random-bred and where possible cogenic lines in assessing the importance of individual factors in infectious immunity.     

不同群系小鼠胚胎玻璃化冷冻保存技术的研究

利用 EFS40 ,二步法对近交系 C5 7BL/6、DBA/2和远交群 ICR小鼠囊胚玻璃化冷冻保存 ,并对冷冻后胚胎体内、外发育效果进行比较。结果表明 ,相同条件下鲜胚经培养 ,近交系 C5 7BL /6小鼠的囊胚发育率 ( 93% )与 ICR( 1 0 0 % )相比差异不显著 ( P>0 .0 5 ) ;而两近交系的囊胚孵化率明显低于 ICR( P<0 .0 1 )。 C5 7BL/6、DBA/2小鼠囊胚冷冻后发育率 ( 93% ,96% )和孵化率 ( 5 2 % ,46% )与各自对照组 ( 1 0 0 % ,1 0 0 %和 61 % ,62 % )相比均无显著差异 ( P>0 .0 5 ) ;并且与 ICR冷冻组发育率和孵化率 ( 94% ,5 3% )之间也无显著差异 ( P>0 .0 5 )。两近交系冻胚移植妊娠与各自对照组和 ICR冷冻组比较均无显著差异 ( P>0 .0 5 )。C5 7BL/6胚胎移植产仔率 ( 35 % )与对照组 ( 5 1 % )之间差异显著 ( P<0 .0 1 ) ,而 DBA/2胚胎移植产仔率 ( 4 7% )与对照组和 ICR冷冻组 ( 39% ,5 8% )相比差异不显著 ( P>0 .0 5 )。     

Mouse strain differences in induction of micronuclei by base analogues and nucleosides

The frequency of induced micronucleated polychromatic erythrocytes (MNPCEs) was compared in BALB/c, C57BL/6, and DBA/2 mice after intraperitoneal (i.p.) injection of 5-bromodeoxyuridine (BUdR), 5-fluorodeoxyuridine (FUdR), cytosine arabinoside (Ara-C), 6-mercaptopurine (6-MP), 5-bromouracil (5-BU), thymidine (TdR), uridine (UdR), adenosine (AdR) and guanosine (GdR). The experimental procedure was a single i.p. injection followed by harvest at 30 h. The frequency of MNPCEs was significantly increased in all strains by treatment with BUdR, FUdR, Ara-C and 6-MP compared to vehicle control. TdR and UdR induced MNPCEs slightly in BALB/c mice but showed no effect on C57BL/6 and DBA/2 mice. 5-BU, AdR, and GdR did not increase the frequency of MNPCEs in any mouse strain used. These results suggest that BALB/c mice are more susceptible to induction of MNPCEs by clastogenic base analogues and nucleosides than are C57BL/6 or DBA/2 mice.     

Characterization of suppressor cells in mice bearing syngeneic mastocytoma.

Suppressor cells from syngeneic P815 mastocytoma-bearing DBA/2 mice that inhibit in vitro generation of specific anti-tumor cytotoxicity were characterized. Suppressive activity was almost completely eliminated by treating suppressive spleen cells with anti-theta serum and complement. Treatment with anti-mouse lg serum and complement or with carbonyl iron did not affect their suppressive activity. When suppressive thymocytes from P815 tumor-bearing DBA/2 mice were tested for their capacity to inhibit the generation of cytotoxicity against L1210 cells, a leukemia line in DBa/2 mice, they did not affect the activity, indicating that the supressor cells in the thymocytes of P815 tumor-bearing mice are specific to the tumor. When Ficoll-Hypaque density cell separation was carried out with cytotoxic spleen cells and suppressive spleen cells from 815 tumor-bearing mice, the dense fraction was enriched for kiler cells whereas the suppressive activitty was mainly recovered in the light fraction. Therefore, killer cells and suppressor cells in P815 tumor-bearing mice are thought to be distinct populations.     

Complement split product C5a mediates the lipopolysaccharide-induced mobilization of CFU-s and haemopoietic progenitor cells, but not the mobilization induced by proteolytic enzymes

Intravenous (i.v.) injection of mice with lipopolysaccharide (LPS), and the proteolytic enzymes trypsin and proteinase, mobilizes pluripotent haemopoietic stem cells (CFU-s) as well as granulocyte-macrophage progenitor cells (GM-CFU) and the early progenitors of the erythroid lineage (E-BFU) from the haemopoietic tissues into the peripheral blood. We investigated the involvement of the complement (C) system in this process. It appeared that the early mobilization induced by LPS and other activators of the alternative complement pathway, such as Listeria monocytogenes (Lm) and zymosan, but not that induced by the proteolytic enzymes, was absent in C5-deficient mice. The mobilization by C activators in these mice could be restored by injection of C5-sufficient serum, suggesting a critical role for C5. The manner in which C5 was involved in the C activation-mediated stem cell mobilization was studied using a serum transfer system. C5-sufficient serum, activated in vitro by incubation with Lm and subsequently liberated from the bacteria, caused mobilization in both C5-sufficient and C5-deficient mice. C5-deficient serum was not able to do so. The resistance of the mobilizing principle to heat treatment (56 degrees C, 30 min) strongly suggests that it is identical with the C5 split product C5a, or an in vivo derivative of C5a. This conclusion was reinforced by the observation that a single injection of purified rat C5a into C5-deficient mice also induced mobilization of CFU-s.     

Complement Split Product C5a Mediates the Lipopolysaccharide-Induced Mobilization of Cfu-S and Haemopoietic Progenitor Cells, But Not the Mobilization Induced By Proteolytic Enzymes

Abstract. Intravenous (i.v.) injection of mice with lipopolysaccharide (LPS), and the proteolytic enzymes trypsin and proteinase, mobilizes pluripotent haemopoietic stem cells (CFU-s) as well as granulocyte-macrophage progenitor cells (GM-CFU) and the early progenitors of the erythroid lineage (E-BFU) from the haemopoietic tissues into the peripheral blood. We investigated the involvement of the complement (C) system in this process. It appeared that the early mobilization induced by LPS and other activators of the alternative complement pathway, such as Listeria monocytogenes (Lm) and zymosan, but not that induced by the proteolytic enzymes, was absent in C5-deficient mice. the mobilization by C activators in these mice could be restored by injection of C5-sufficient serum, suggesting a critical role for C5.
The manner in which C5 was involved in the C activation-mediated stem cell mobilization was studied using a serum transfer system. C5-sufficient serum, activated in vitro by incubation with Lm and subsequently liberated from the bacteria, caused mobilization in both C5-sufficient and C5-deficient mice. C5-deficient serum was not able to do so. the resistance of the mobilizing principle to heat treatment (56°C, 30 min) strongly suggests that it is identical with the C5 split product C5a, or an in vivo derivative of C5a. This conclusion was reinforced by the observation that a single injection of purified rat C5a into C5-deficient mice also induced mobilization of CFU-s.     

DNA-ase I activity in the DNA-ase I-inhibitor system

An increase in the DNase I activity was revealed in the serum of mice after intraperitoneal injection of different antigens. This reaction is related to the antigen nature and is dissimilar in mice of different strains. The increased activity of the inhibitor in the spleen of DBA/2 and BALB/c mice was discovered after intravenous injection of bovine DNase I. A potential role of serum DNase I in the system DNase I-inhibitor is discussed.     

Observations on soft tissue calcification in DBA/2NCrj mice in comparison with CRJ:CD-1 mice

Male and female DBA/2NCrj (DBA/2) mice 3, 4, 5 and 10 weeks old were examined biochemically and pathologically and the results obtained were compared with those for CRJ:CD-1 (ICR) mice of the same age. The plasma levels of glucose, triglyceride and total cholesterol tended to be lower in DBA/2 mice than in ICR mice but the levels of non-esterified fatty acid, calcium and inorganic phosphorus were almost the same in the two strains. The mean body weight of DBA/2 mice was significantly lower than that of ICR mice at each examination, and the relative weights of the hearts of male and female DBA/2 mice were significantly greater than those of male and female ICR mice. Cardiac calcinosis, tongue calcification and corneal degeneration occurred exclusively in DBA/2 mice with incidences of 30%-100%. The incidence and severity of these lesions increased with age but no sex differences were seen. It was difficult to relate differences in biochemical features of the two strains with pathological findings obtained in the DBA/2 mice. The numbers of cells secreting adrenocorticotropic hormone in the pituitary glands were significantly greater in male and female DBA/2 mice than in ICR mice, suggesting a higher secretion of corticosteroids in the former strain.     

不同品系小鼠对代谢性高尿酸血症造模的影响

目的：分别以昆明种小鼠及ICR、C57BL/6J小鼠为研究对象,比较在复制高尿酸血症模型时可能的小鼠品系差异,并通过降尿酸药物别嘌呤醇与非布索坦验证选择降尿酸药物筛选时选用不同品系动物造模的影响。方法：采用不同剂量次黄嘌呤腹腔注射联用尿酸酶抑制剂氧嗪酸钾皮下注射给药,测定不同造模时段各品系小鼠血清尿酸值。结果：ICR、C57BL/6J小鼠对高尿酸血症造模耐受显著高于昆明种小鼠,在腹腔注射次黄嘌呤500mg/kg,皮下注射氧嗪酸钾300mg/kg时,才可获得稳定的可用于药物筛选的高尿酸血症模型。结论：选择高尿酸血症在体模型时,昆明种小鼠灵敏度高于ICR小鼠以及近交系的C57BL/6J小鼠。     

Strain differences in histamine release from mouse peritoneal mast cells induced by compound 48/80 or A23187

Strain differences among BALB/c, BDF1, CDF1, C3 H/He, C57 BL/6, DBA/2, ddy and ICR mice were investigated with respect to the ratios of histamine release from mouse peritoneal mast cells induced by compound 48/80, a Ca2+ dependent histamine releaser, and the Ca2+ ionophore A23187. The ratios of histamine release from mouse peritoneal mast cells induced by compound 48/80 were found to be high in BALB/c, ddY and ICR mice, but low in BDF1, CDF1, C3 H/He, C57 BL/6 and DBA/2 mice. Those induced by Ca2+ ionophore A23187 were high in BALB/c, BDF1, CDF1, C3 H/He, DBA2, ddy and ICR mice but low in C57 BL/6 mice. These results indicate that differences in histamine release from mouse peritoneal mast cells are strain dependent.     

Anti-tumor effects of an antiserum raised in syngeneic mice to a tumor-specific T suppressor factor

Summary DBA/2 mice inoculated with either cells from the syngeneic P815 tumor or tumor cell membrane extracts develop T suppressor cells which suppress the in vitro generation of cytotoxic T lymphocytes with specificity for the tumor. A soluble suppressor factor with similar properties can be isolated from suppressor cell-enriched populations. It can be highly purified by appropriate immunoadsorption. Antisera to this suppressor factor raised in either DBA/2 or C57BL/6 mice can specifically absorb out suppressor factor and eliminate suppressor cells in the presence of complement. The in vivo effects of these antisera were tested for their ability to modulate the growth of P815 tumors in DBA/2 mice. It was found that the antiserum raised in syngeneic (DBA/2) but not allogeneic (C57BL/6) mice was able to significantly slow the rate of tumor growth and to prolong survival in treated mice. The antiserum was effective in this way only if it was administered early in the course of tumor growth. It was shown that this effect was not attributable to the presence in the serum of antibodies directed to antigens present on P815 cells, and it therefore appears to be due to interference with the function of T suppressor cells arising early in the immune response to the tumor cells.     

Bothrops asper snake venom and its metalloproteinase BaP-1 activate the complement system. Role in leucocyte recruitment

The venom of the snake Bothrops asper, the most important poisonous snake in Central America, evokes an inflammatory response, the mechanisms of which are not well characterized. The objectives of this study were to investigate whether B. asper venom and its purified toxins--phospholipases and metalloproteinase--activate the complement system and the contribution of the effect on leucocyte recruitment. In vitro chemotaxis assays were performed using Boyden's chamber model to investigate the ability of serum incubated with venom and its purified toxins to induce neutrophil migration. The complement consumption by the venom was evaluated using an in vitro haemolytic assay. The importance of complement activation by the venom on neutrophil migration was investigated in vivo by injecting the venom into the peritoneal cavity of C5-deficient mice. Data obtained demonstrated that serum incubated with crude venom and its purified metalloproteinase BaP-1 are able to induce rat neutrophil chemotaxis, probably mediated by agent(s) derived from the complement system. This hypothesis was corroborated by the capacity of the venom to activate this system in vitro. The involvement of C5a in neutrophil chemotaxis induced by venom-activated serum was demonstrated by abolishing migration when neutrophils were pre-incubated with antirat C5a receptor antibody. The relevance of the complement system in in vivo leucocyte mobilization was further demonstrated by the drastic decrease of this response in C5-deficient mice. Pre-incubation of serum with the soluble human recombinant complement receptor type 1 (sCR 1) did not prevent the response induced by the venom, but abolished the migration evoked by metalloproteinase-activated serum. These data show the role of the complement system in bothropic envenomation and the participation of metalloproteinase in the effect. Also, they suggest that the venom may contain other component(s) which can cause direct activation of C5a.     

Strain difference in mouse natural killer activity augmented by mouse interferon and poly I.C

The level of natural killer (NK) activity was found to vary considerably among several mouse strains. In vivo and in vitro, interferon (IFN) and IFN inducers have been shown to augment mouse NK activity. C3H/He mice showed high NK activity, DDD/1 and A/J mice low NK activity, and C57BL/6, BALB/c and DBA/2 mice intermediate NK activity after injection with polyinosinic polycytidylic acid (poly I. C.). The same NK activity correlation was observed in nontreated mice, but the NK activities were lower compared with the poly I. C.-injected mice. Moreover, the DDD/1 and A/J mice showed almost no augmentation of NK activity on injection with poly I.C. In vivo, C3H/He, BALB/c and C57BL/6 mice injected with IFN showed augmented NK activity, but DDD/1 mice showed no such reaction. In vitro, C3H/He, BALB/c and C57BL/6 mouse spleen cells treated with IFN also showed augmented NK activity, but DDD/1 mouse spleen cells showed almost none. F1 hybrids between high (C3H/He) and low (DDD/1) NK-activity strains showed high NK activity. Thus, activity is dominant over low activity. The segregation of (DDD/1 X C3H/He) Fl X DDD/1 back-cross mice suggested that the strain differences in NK activity are under polygenic control.     

Anesthetic Effects of a Mixture of Medetomidine,Midazolam and Butorphanol in Two Strains of Mice

The combination of ketamine and xylazine is a widely used anesthetic for laboratory animals. However, due to an abuse problem in Japan, ketamine has been specified as a narcotic since 2007. Instead of using ketamine, Kawai et al. reported an injectable formula with an equivalent effect to the mixture of ketamine and xylazine [11]. The mixture of 0.3 mg/kg body weight (b.w.) medetomidine (Med.), 4.0 mg/kg b.w. midazoram (Mid.), and 5.0 mg/kg b.w. butorphanol (But.) produced an anesthetic duration of around 40 min in outbred ICR mice. However, the anesthetic effect of the mixture for inbred mice strains remains unknown. Therefore, we examined anesthetic effects of the mixture of Med., Mid., and But. in the BALB/c and C57BL/6J strains. After intraperitoneal injection into mice, right front paw, left hind paw, and tail pinch reflexes as well as corneal and righting reflexes were observed. Every 5 min, we scored each reflex category as 0 for reaction or 1 for no reaction. As long as the total score was at least 4 out of 5, we considered the mixture as putting a mouse in a surgical anesthetic state. The mixture produced an anesthetic duration of more than 45 min in both strains of mice. These results indicate that the mixture of Med., Mid., and But. can be a useful and effective anesthesia for the BALB/c and C57BL/6J strains of inbred mice as well as outbred ICR mice.     

Platelet-activating factor produces shock, in vivo complement activation, and tissue injury in mice

We previously showed that TNF and endotoxin (LPS) synergize to activate the complement system and produce shock and bowel injury in normal mice. However, C5-deficient mice were protected from these adverse effects. In this study, we show that in mice, platelet-activating factor (PAF) antagonist prevents TNF- and LPS-induced complement activation, bowel injury, and death, indicating that PAF mediates the actions of TNF and LPS. We then examined the role of the complement system in PAF-induced shock and tissue injury. We found that 1) PAF (3 micrograms/kg) induces shock, hemoconcentration, bowel necrosis, and death in normal mice, whereas C5-deficient mice are protected from these effects. (Protection was abrogated when the dose of PAF was raised to 5 micrograms/kg.) Furthermore, when C5-deficient mice were reconstituted with normal serum, they also developed shock, bowel injury, and death in response to PAF. Thus, C5 is required for PAF to induce injury. 2) PAF activates the complement system in vivo, but not in vitro. The mechanism of complement activation by PAF is unclear. Inasmuch as PAF stimulates neutrophils to release protease that may activate the complement system, we examined the effect of neutrophil depletion on PAF-induced injury and complement activation. We found that neutrophil depletion fails to prevent PAF-induced complement activation, although PAF-induced lethality is much reduced. We conclude that PAF causes complement activation, and acts in synergy with active complement fragments to produce shock and tissue injury. Neutrophils probably do not play the pivotal role in PAF-induced complement activation.     

Modulation of natural killer activity in mice following infection with Listeria monocytogenes

Mice that received a sublethal, intraperitoneal dose of viable Listeria monocytogenes, virulent strain 10403, exhibited a systemic increase in natural killer (NK) activity. The kinetics of the response differed with respect to the various effector cell populations analyzed. Resident peritoneal cells and peripheral blood leukocytes demonstrated high NK activity on Days 3, 7, and 10. Peak spleen and bone marrow NK activity was observed on Day 3, returning to normal levels by Day 7. In contrast, peritoneal exudate cells, elicited with proteose peptone, expressed enhanced NK activity for 60 days following infection with viable Listeria. Augmented NK activity was detected with all cell types as early as 12 hr after infection. The intraperitoneal injection of nonviable antigenic preparations derived from L. monocytogenes, strain 10403, resulted in the enhancement of peritoneal and splenic NK activity. In contrast, mice that received an intraperitoneal injection of avirulent Listeria, strain 19113, failed to express enhanced levels of NK activity. The genetic trait of anti-listerial resistance which is associated with non-H-2 linked genes was of no importance with respect to enhanced NK activity. Listeria-resistant C57BL/6J and Listeria-susceptible DBA/2J mice both produced systemic augmentation of NK activity following infection. NK activity was not abrogated by macrophage depletion or by treatment with anti-Thy 1.2 serum plus complement. These results confirm the potent immunostimulatory capacity of virulent Listeria for NK activity and provide further insight into the kinetics of this response in various lymphoid compartments. The protracted augmentation of NK activity of elicited peritoneal exudate cells as compared to nonelicited peritoneal cells in Listeria-primed mice suggests that the influx of inflammatory cells may provide NK-enriched and/or accessory populations for immunopotentiation of NK activity in inflammatory sites.     

Autoimmunization in murine graft-vs-host disease. I. Selective production of antibodies to histones and DNA

A lupus-like disease characterized by a severe immune complex glomerulonephritis and IgG autoantibody production was induced in (C57BL/6 X DBA/2)F1 mice by injection of parental DBA/2 lymphoid cells. The ensuing graft-vs-host (GVH) reaction resulted in a 10- and a 100-fold increase in serum IgG antibody levels to denatured DNA and total histones, respectively, compared with that in F1----F1 control mice. The level of anti-DNA antibodies peaked 2 wk after injection of DBA/2 cells and preceded peak anti-histone levels by approximately 2 wk. Anti-histone antibodies were generated predominantly to histones H1, H2A, and H2B, a profile different from that observed in NZB/NZW and MRL-lpr/lpr mice. The marked increase in IgG antinuclear antibodies did not correlate with increases in total IgG serum levels and was not associated with comparable increases in antibodies to transferrin, hemoglobin, fibrinogen, or thyroglobulin. Selective autoantibody production was also observed in vitro, wherein GVH spleen cells produced high levels of IgG antibodies to total histones and denatured DNA but not to these non-nuclear protein antigens. In contrast, spleen cells stimulated in vitro with lipopolysaccharide produced equivalent amounts of antibodies to all antigens tested. Our results are in agreement with those of other investigators and collectively suggest that IgG autoantibodies in GVH disease, and possibly in spontaneous lupus-like disease, are not secondary to a generalized B cell activation, but may be selectively generated in response to self antigens with unique configurational properties.     

Inhibition on Proteasome β1 Subunit Might Contribute to the Anti-Cancer Effects of Fangchinoline in Human Prostate Cancer Cells

Fangchinoline is a bisbenzylisoquinoline alkaloid isolated from Radix Stephaniae tetrandrae S. Moore. Fangchinoline and its structure analogue, tetrandrine, exhibited direct binding affinity with recombinant human proteasome β1 subunit and also inhibited its activity in vitro. In cultured prostate PC-3 cells and LnCap cells, fangchinoline could dose-dependently inhibit cell proliferation and caspase-like activity of cellular proteasome which was mediated by proteasome β1 subunit. The inhibitive effect of fangchinoline on caspase-like activity of proteasome was also observed in purified human erythrocyte 20S proteasome. In PC-3 cells, fangchinoline induced cell cycle arrest at G0/G1 phase and apoptosis. Treatment of PC-3 tumor-bearing nude mice with fangchinoline inhibited tumor growth, induced apoptosis and also caused decrease in proteasome activities in tumor xenografts. Dose-dependent and time-dependent accumulation of ubiquitinated proteins and important proteasome substrates such as p27, Bax and IκB-α were observed in fangchinoline-treated cells. Over-expression of proteasome β1 subunit by plasmid transfection increased sensitivity of cells to the cytotoxicity of fangchinoline while knockdown of proteasome β1 subunit ameliorated cytotoxicity of fangchinoline in PC-3 cells. Results of the present study suggested that proteasome inhibition was involved in the anti-cancer effects of fangchinoline. Fangchinoline and its structure analogues might be new natural proteasome inhibitors targeting β1 subunit.     

Sensitivity of the splenic immunocompetent cells of mice with different genotypes to the action of alkylating agents

It has been established in experiments in vitro that splenocytes of DBA/2GSto mice are more sensitive to the immunosuppressant action of the alkylating agents (cyclophosphamide, sarcolysine and thiophosphamide) than splenocytes of BALB/cGLacSto mice. Splenocytes of C3H/SnRap mice exhibit and intermediate type of sensitivity. T-lymphocytes of the spleen of BALB/cGLacSto and DBA/2GSto mice are more sensitive in vitro to the action of active metabolites of cyclophosphamide as compared to B-lymphocytes, with both types of the cells of DBA/2GSto mice being affected to a greater extent than the cells of BALB/cGLacSto mice.