Hybrid Mouse Strain Research Articles

Serum glucose, glucose tolerance, corticosterone and free fatty acids during aging in energy restricted mice

Energy restriction, the only method known to increase maximum life span in laboratory animals, was used as a tool to test hypotheses regarding possible mechanisms of aging. Serum glucose and corticosterone (CS) concentrations in mice of a long-lived hybrid mouse strain, aged 7, 17, and 29 months, and on 50%, 80%, and 100% of ad libitum intake, were measured. Serum glucose and CS concentrations were also measured in response to intraperitoneal (i.p.) glucose challenge in mice at ages 7 and 29 months. Serum glucose and CS concentrations were also measured at several time points over 36 h, to assess their diurnal variation. There were no differences in single fasting glucose concentrations in 7- and 29-month-old mice at the same degree of energy restriction, but energy restriction decreased glucose concentrations. Serum CS concentrations were generally increased restricted animals with respect to fully fed ones. Average serum glucose concentrations were found to be significantly decreased by dietary restriction. Glucose tolerance curves were unchanged by age in ad libitum fed or 50% restricted animals, but in 80% ad libitum groups, older animals showed evidence of decreased glucose tolerance with respect to young animals. For each age, peak serum glucose concentrations after i.p. glucose loading varied with degree of energy restriction, with more severely restricted animals showing less glucose tolerance. Average serum CS concentrations were elevated at 7 months by restriction, especially at night and long after feeding, but we found no differences with age or diet in average CS concentrations. Our serum glucose results support the hypothesis that nonenzymatic glycation is mechanically involved in normal aging. Our serum CS results do not support the hypothesis that CS contributes significantly to the pathophysiology of normal aging in mice.

Temporal effects of ouabain on in-vitro development of mouse zygotes.

Ouabain is a specific inhibitor of Na(+)-K(+)-ATPase, an enzyme which controls the intracellular Na+ and K+ levels. In this study, in-vitro fertilized zygotes from a hybrid mouse strain were used to examine the temporal effects of 50 microM ouabain on embryonic development in vitro during the preimplantation period. A higher incidence of blastocyst formation at the end of the culture period was found when embryos were cultured in the presence of ouabain from 22 to 46 h post-insemination, or any other period that included this time period. When zygotes from randomly bred mice were used, inhibition of Na(+)-K(+)-ATPase with ouabain clearly promoted development through the 2-cell block in vitro. As Na(+)-K(+)-ATPase is the most important regulator of intracellular electrolyte concentrations in mammalian cells, these results suggest that an ionic imbalance exists in embryos cultured in conventional media which can be positively influenced by inhibiting this enzyme.

Temporal effects of taurine on mouse preimplantation development in vitro.

Previously it has been shown that significantly more 2-cell mouse embryos reach the blastocyst stage when cultured in medium supplemented with taurine. In this study, in-vitro fertilized zygotes from a hybrid mouse strain were used to examine the temporal effects of 10 mM taurine on embryonic development in vitro during the preimplantation period. Taurine exerted its beneficial effect exclusively during the first 2 days post-insemination. The effect of taurine on blastocyst formation appeared to be restricted mostly to the period 20-48 h after fertilization, during which time mouse embryos are at the two-cell stage. Although more blastocysts were found when embryos were cultured in taurine-containing medium from 5 to 20 h post-insemination, this difference was not significant compared to the number of blastocysts when embryos were cultured without taurine. Taurine did not appear to affect the two-cell block of mouse embryos from random-bred strains.

Protection by WR-151327 against Late-Effect Damage from Fission-Spectrum Neutrons

The mutagenic and carcinogenic properties of fission-spectrum neutrons (KERMA-weighted mean energy of 0.85 MeV) from Argonne National Laboratory's JANUS reactor are substantially greater than those of low-LET radiation sources such as X-ray and 60Co photons. However, in contrast to the vast amount of work focused on chemical protection against damage induced by low-LET radiation, studies on the prevention of carcinogenic damage induced by fission neutrons have been limited. We have investigated the protective properties of the thiophosphorate compound S-3-(3-methylaminopropylamino)propylphosphorothioic acid (WR-151327) against carcinogenesis and life shortening in the B6CF1 hybrid mouse strain. Male and female mice, 200 of each sex per experimental group, were irradiated individually at 110 days of age. WR-151327 was administered intraperitoneally at a dose of 580 mg/kg 30 min prior to irradiation with a dose of 10 cGy. Animals were housed five to a cage; cage locations in holding rooms were controlled by computer and randomized. Mice were checked daily and all deceased animals were necropsied. A neutron dose of 10 cGy significantly altered the patterns of death of male and female animals compared to corresponding unirradiated control groups (logrank P values of 0.01 and 0.07, respectively). This was evidenced by a shortening of the life span due to tumor induction in the irradiated groups. WR-151327, when administered 30 min prior to irradiation, effectively protected both male and female animals from these effects. The life curves of irradiated male and female animals and those of corresponding unirradiated control groups were not significantly different (logrank P values of 0.63 and 0.25, respectively).

Effect of imexon treatment on friend virus complex infection using genetically defined mice as a model for HIV-1 infection

Imexon (4-imino-1,4-diazobicyclo-3.1.0-hexan-2-one) was moderately effective in the treatment of a retroviral infection in a genetically defined murine model. The animal model consisted of a Friend virus complex (FV) infection in a hybrid mouse strain, (B10.A × A/WySn)F 1, which has similarities with acquired immune deficiency syndrome (AIDS). Intraperitoneal imexon initiated 1 or 3 days after FV inoculation and continued through 13 days after inoculation significantly reduced splenomegaly, splenic cell-free virus titers and viral RNA. Viral infectious centers/10 6 splenocytes and FV titers in the plasma were reduced, though not to a statistically significant level. The effect of imexon on survival was not statistically significant which suggested that the antiviral effects were only transiently effective. Phytohemagglutinin-induced blastogenesis and percent of total T cells, T helper cells and T suppressor/cytotoxic cells in the spleens were increased, and the percentage of B cells decreased by imexon treatment of both FV-infected and uninfected mice. The splenic natural killer cell activity and interleukin-1 production were not markedly affected. Virus specific neutralizing antibody developed in both imexon- and placebo-treated FV-infected mice, although titers were lower in the imexon-treated animals.

Chimeric Analysis of the Site of Lurcher Gene Action with Respect to Glial Enzyme Expression

Immunocytochemical analysis of aggregation chimeras made using either of the mutants, Lurcher or Purkinje cell degeneration, previously showed that only Bergmann glia close to surviving Purkinje cells expressed an apparently normal level of the enzyme, glycerol-3-phosphate dehydrogenase (GPDH) (Fisher and Mullen, 1988). In the present study, aggregation chimeras were made using embryos from a B6D2 hybrid mouse strain carrying the Lurcher (Lc/+) mutation and homozygous for an allele specifying a high level of beta-glucuronidase activity and embryos from a wild-type C3H strain with low beta-glucuronidase activity. Chimeric cerebella were analyzed immunocytochemically and histochemically to determine whether Lurcher mutant Bergmann glia could express a normal, high level of GPDH. Comparisons between pairs of alternately stained, 2 microns thick serial sections showed that Bergmann glia with high level of beta-glucuronidase (i.e., Lurcher) expressed normal GPDH immunoreactivity only when close to surviving, wild-type Purkinje cells. Interestingly, in Purkinje cell-free areas of cerebellar cortex that were sufficiently large that GPDH expression was diminished, Bergmann glia also showed a reduced level of histochemically detectable beta-glucuronidase activity, as do Bergmann glia in adult Lc/+ mice. The results indicate that Lc/+ mutant Bergmann glia are not intrinsically defective with regard to expression of the enzymes, GPDH and beta-glucuronidase, but rather, expression of these enzymes depends on glial interaction with wild-type Purkinje cells.

Teratology of 2,3,7,8-tetrachlorodibenzo- p-dioxin in a complex environmental mixture from the Love Canal

The organic phase of a leachate (OPL) from the Love Canal chemical dump site contains more than 100 organic compounds including 2,3,7,8-Tetrachlorodibenzo- p-dioxin (TCDD). The teratogenic potential of OPL was determined in two inbred and one hybrid mouse strain which differ in their sensitivity to aromatic hydrocarbon ( Ah) receptor-mediated toxicity. OPL was orally administered in corn oil on Days 6–15 of gestation to C57BL 6 J mice ( Ah b Ah b ) at doses of 0, 0.1, 0.3, 0.5, and 0.7 g kg −1 day −1 and to DBA 2 J ( Ah d Ah d ) females, which were mated with either DBA 2 J or C57BL 6 J males, at 0, 0.5, 1, and 2.0 g kg −1 day −1. In C57BL 6 J mice, which express a high-affinity Ah receptor that avidly binds TCDD, the ED50's of OPL for cleft palate and hydronephrosis were 0.44 and 0.11 g OPL kg −1 day −1, respectively. Maternal mortality was 5% at the highest dose. In DBA 2 J fetuses, which express a low-affinity receptor, neither treatment-related cleft palate nor hydronephrosis was induced by dose levels that caused 36% maternal mortality. In hybrid D2B6F1 fetuses, the incidence of cleft palate reached only 8% at 2 g OPL kg −1 day −1 but the ED50 for hydronephrosis was 0.76 g OPL kg −1 day −1. TCDD was similarly administered to pregnant C57BL 6 J mice at 0, 0.5, 1, 2, and 4 μg kg −1 day −1 and to DBA 2 J mice at 0, 0.5, 2, 4, and 8 μg kg −1 day −1. In C57BL 6 J fetuses, the ED50's for cleft palate and hydronephrosis were 4.6 and 0.73 μg TCDD kg −1 day −1, respectively. In DBA 2 J fetuses the ED50's for cleft palate and hydronephrosis were 15.0 and 6.4 μg TCDD kg −1 day −1, respectively. Both the OPL and TCDD caused maternal hepatomegaly and thymic atrophy in all strains, but increased only C57BL 6 J fetal weights. OPL decreased the number of fetuses per C57BL 6 J dam at the two highest doses but there were no other reproductive effects in any of the groups. It was concluded that the OPL is teratogenic and that hydronephrosis is a sensitive measure of TCDD toxicity in a complex organic mixture. Based on the ED50's of OPL- and TCDD-induced cleft palate and hydronephrosis in the C57BL 6 J strain, the OPL had TCDD equivalence of 6.6 and 10.5 ppm, respectively. These values compare closely with the chemical analysis of 3 ppm. The results suggest that the teratologic effects are due primarily to the TCDD in the OPL and that these effects are mediated through the Ah receptor, but that the maternal thymic atrophy and hepatomegaly were due primarily to the non-TCDD components of the OPL.

Immunological relationships during primary infection with Heligmosomoides polygyrus (Nematospiroides dubius): expulsion of adult worms from fast responder syngeneic and hybrid strains of mice.

The time-course of low and high intensity primary infections with Heligmosomoides polygyrus was monitored in SJL and SWR mice, both of which usually expel worms within 7 weeks of larval administration. Worm expulsion in these strains was not dependent on the intensity of infection, with low and high intensity worm burdens being lost within the same period of time. The ability to expel worms rapidly was inherited in a dominant manner in F1 offspring of SJL or SWR mice mated with C57Bl10 mice; the latter being a strain in which no loss of worms was evident within 10 weeks of infection. However, neither (SJL x C57Bl10)F1 nor (SWR x C57Bl10)F1 mice expelled worms as rapidly as the parental SJL and SWR strains. (SWR x B10G)F1 [H-2q] mice eliminated worms faster than (SWR x C57Bl10)F1 [H-2bq], suggesting that the b haplotype had a moderating influence on the expulsion process. In fact (SWR x B10G)F1 mice showed a significant reduction in worm burdens by week 4 but by weeks 6-8 the rate of worm loss had slowed considerably. In contrast, SJL and SWR mice, whilst initiating rejection slightly later, (after week 4) expelled all worms within the following 2 weeks. Thus two distinct patterns of response were observed among the fast responder strains as exemplified by SWR and SJL mice on the one hand and (SWR x B10G)F1 on the other. Our results support the hypothesis that the course of a primary infection with H. polygyrus is influenced by multiple host gene loci, some of which are encoded within the MHC. SJL and SWR mice probably have similar if not identical gene combinations at loci which determine a fast responder phenotype, distinguishing them from the other mouse strains which have been studied.

The EFF the effect of dietary restriction of MYC protooncogene expression in mice: A preliminary study

The effect of chronic dietary restriction on the expression of the c-myc protooncogene was determined in the livers of a hybrid mouse strain (C57B16 × C3H F1 hybrid) at three time points during a 24-h period: 1 h after lights on (1 HALO), 5 h prior to feeding (12 HALO), and 2 h after feeding (19 HALO). In addition, in whole animals studies, changes in core body temperature were monitored. In mice which had been subjected to a chronic diet restriction (60% of the intake of ad libitum controls), c-myc expression was significantly reduced at 1 HALO and 19 HALO compared to corresponding ad libitum animals. In addition, significant differences in c-myc expression were found between time points, in both the ad libitum and restricted groups, suggesting that myc protooncogene expression in the liver may be regulated in a circadian fashion. C-myc expression may correlate with body temperature, suggestng a possible association with metabolic output.

Teratology of 2,3,7,8-Tetrachlorodibenzo-p-dioxin in a Complex Environmental Mixture from the Love Canal

The organic phase of a leachate (OPL) from the Love Canal chemical dump site contains more than 100 organic compounds including 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD). The teratogenic potential of OPL was determined in two inbred and one hybrid mouse strain which differ in their sensitivity to aromatic hydrocarbon (Ah) receptor-mediated toxicity. OPL was orally administered in corn oil on Days 6–15 of gestation to C57BL/6J mice (Ahb/ Ahb) at doses of 0, 0.1, 0.3, 0.5, and 0.7 g kg−1 day−1 and to DBA/ZJ (Ahd/Ahd) females, which were mated with either DBA/2J or C57BL/6J males, at 0, 0.5, 1, and 2.0 g kg−1 day−1. In C57BL/6J mice, which express a high-affinity Ah receptor that avidly binds TCDD, the ED50's of OPL for cleft palate and hydronephrosis were 0.44 and 0.11 g OPL kg−1 day−1, respectively. Maternal mortality was 5% at the highest dose. In DBA/2J fetuses, which express a low-affinity receptor, neither treatment-related cleft palate nor hydronephrosis was induced by dose levels that caused 36% maternal mortality. In hybrid D2B6F1 fetuses, the incidence of cleft palate reached only 8% at 2 g OPL kg−1 day−1 but the ED50 for hydronephrosis was 0.76 g OPL kg−1 day−1. TCDD was similarly administered to pregnant C57BL/6J mice at 0, 0.5, 1, 2, and 4 μg kg−1 day−1 and to DBA/2J mice at 0, 0.5, 2, 4, and 8 μg kg−1 day−1. In C57BL/6J fetuses, the ED50's for cleft palate and hydronephrosis were 4.6 and 0.73 μg TCDD kg−1 day−1, respectively. In DBA/2J fetuses the ED50's for cleft palate and hydronephrosis were 15.0 and 6.4 μg TCDD kg−1 day−1, respectively. Both the OPL and TCDD caused maternal hepatomegaly and thymic atrophy in all strains, but increased only C57BL/6J fetal weights. OPL decreased the number of fetuses per C57BL/6J dam at the two highest doses but there were no other reproductive effects in any of the groups. It was concluded that the OPL is teratogenic and that hydronephrosis is a sensitive measure of TCDD toxicity in a complex organic mixture. Based on the ED50's of OPL- and TCDD-induced cleft palate and hydronephrosis in the C57BL/6J strain, the OPL had TCDD equivalence of 6.6 and 10.5 ppm, respectively. These values compare closely with the chemical analysis of 3 ppm. The results suggest that the teratologic effects are due primarily to the TCDD in the OPL and that these effects are mediated through the Ah receptor, but that the maternal thymic atrophy and hepatomegaly were due primarily to the non-TCDD components of the OPL.

Genetic differences in oxygen toxicity are correlated with cytochrome P-450 inducibility.

Susceptibility to oxygen toxicity was studied in three inbred and two hybrid strains of mice. Because in vitro studies have shown that the cytochrome P-450 enzymes can produce oxygen radicals and H2O2, we tested the hypothesis that inducibility of these enzymes might play a role in oxygen toxicity. Mice responsive to hepatic microsomal enzyme induction by aromatic hydrocarbons [C3H/HeJ, C3H/HeN, C3H/HeJ X DBA/2J (designated C3D2F1/J), C3H/HeN X DBA/2J (designated C3D2F1/N)] were more sensitive to the toxic effects of 100% oxygen exposure than were genetically unresponsive mice (DBA/2J). DBA/2J mice survived significantly longer exposure periods with less lung damage. Lung and liver cytochrome P-450 levels increased 2-to 3-fold in C3H and F1 mice during 100% oxygen exposure (maximum levels at 72-96 hr) and subsequently fell prior to death. No increases were seen in cytochrome P-450 levels in DBA/2J mice. Metabolic pathways involving cytochrome P-450 enzymes may initiate or modulate oxidative damage due to oxygen radicals. The difference in responsiveness of mice to microsomal enzyme induction may imply genetic differences in susceptibility to oxidative stress, may help to explain species differences in susceptibility, and may have long-term implications in therapeutics and patient care if similar inherited differences exist in humans.

A morphologic classification of brain tumors found in several strains of mice.

Brain tumors were found in 42 mice from a total study population of 77,410 mice, which included several strains (BALB/c, C3H, C57BL/6, and hybrids of these strains). The brain tumors were classified on the basis of the new World Health Organization classification of human brain tumors. Tumors originated from neuroepithelial and meningeal tissues, blood vessels, and germ cells. The youngest animal with a tumor was 111 days of age. The tumor incidence was low, being 0.054% of the total study population, with 0.067% in controls and 0.052% in treated mice. Lipomas were the most common type of tumor diagnosed, and they were considered to represent hamartomas rather than true neoplasms. There were 27 brain tumors other than lipomas, the majority (16) of which occurred in BALB/c mice, whereas meningeal tumors (6) were confined to C3H and hybrid strains of mice. The morphologic characteristics of each tumor type are presented.

Differences in liver ganglioside patterns in various inbred strains of mice

The ganglioside patterns in the liver of different inbred and hybrid strains of mice were investigated. The inbred strains were Balb/cAnNCr1BR, C57BL/6NCr1BR, DBA/2NCr1BR. C3H/HeNCr1BR; the hybrid strain was the Swiss albino. The following major gangliosides were found to be present in mouse liver: GM3-NeuAc; GM3-NeuGl, GM2 [a mixture of one species carrying N-acetylneuraminic acid (NeuAc) and one carrying N-glycollylneuraminic acid (NeuGl)], GM1 and GD1a-(NeuAc,NeuGl). The qualitative and quantitative patterns of liver gangliosides were markedly different in the various inbred strains of mice; in Balb/cAnNCr1BR strain, ganglioside GM2 was preponderant (99.2% of total ganglioside content); in C57BL/6NCr1BR, the major ganglioside was GM2 (90.4%), followed by GM3-NeuAc (5.6%) and GM3-NeuGl (4.0%); in DBA/2NCr1BR, GM2 accounted for 77.1%, GD1a-(NeuAc,NeuGl) 18.9% and GM1 3.1% of gangliosides; in C3H/HeNCr1BR, GM2 constituted 50.6%, GM1 22.8% and GD1a-(NeuAc,NeuGl) 22.1%. In the hybrid Swiss albino mice, liver ganglioside composition markedly varied from one animal to another, GM3-NeuGl, GM2 and GD1a-(NeuAc,NeuGl) being the predominant gangliosides in the various cases.

Comparison of strains and culture media used for mouse in vitro fertilization

AbstractSuccess rates of superovulation in response to gonadotropic hormone treatment and in vitro fertilization (ie, mitotic cleavage following insemination) of mouse eggs from outbred CD‐1, hybrid CB6Fl, or hybrid B6CBAF1, mice were compared using either a mouse inseminationmedium, modified Krebs‐Ringer‐bicarbonate (m‐KRB), or a human insemination medium, Ham's F10 nutrient mixture. Inseminations were performed in either organ culture dishes or screw‐top, flat‐side tissue culture tubes. Mean superovulation rates (± SD) were 24.2 (5.1) for CD‐1, 33.0 (5.8) for CB6F1, and 16.3 (6.6) for B6CBAF1 mice. For in vitro cleavage the best combination of mouse strain, insemination medium, and culture container was achieved using CB6F1, mice, m‐KRB medium, and culture tubes. However, Ham's medium used with either hybrid mouse strain was shown to be employable for fertilization of mouse eggs in vitro as a quality control assay and/or experimental model system for testing the human in vitro fertilization procedure.

The relationship of genotype, sex, body weight, and growth parameters to lifespan in inbred and hybrid mice

Data from nine inbred and six hybrid mouse strains of both sexes were used in a correlational analysis to examine the relationships between lifespan and several growth parameters, including body weight at weaning, at 6 weeks after weaning, and at 1 year, and estimates of growth rate, food consumption, and feeding efficiency during early life. The analysis revealed strong relationships of genotype to all variables. Hybridization was associated with longer lifespan, but sex was not related to lifespan. Several growth parameters were significantly related to lifespan, but the directions of the correlations were sex-dependent. Several body weight and growth parameters were positively correlated to lifespan in males, while negatively correlated to lifespan in females. Genotype accounted for most of the variance in these relationships with the exception of hybrid males, where the correlation between growth rate and lifespan was attributable largely to environmental factors. In demonstrating significant correlations between lifespan and constitutional variables within a species, the results supported a morphogenetically based hypothesis of lifespan inheritance; however, the sex differential in the direction of the relationship between growth and lifespan further demonstrated the difficulty of making predictions deduced from the hypothesis.

Single gene control of resistance to cutaneous leishmaniasis in mice.

A series of inbred, congenic resistant, and hybrid strains of mice were intradermally inoculated with 10(6) promastigotes of Leishmania tropica. These mice were divided into susceptible and resistant groups using the criteria of lesion size, development of metastatic foci and skin-test reactivity. At 16 weeks of infection, resistant strains A/J, DBA/1J, AKR/J, CBA/J, C3H/HeJ, NZB/BINJ, C57BL/6J, C57BL/10Sn, B10.D2, B10.129(10M), and B10.CE(30NX) had completely resolved their lesions, while susceptible SWR/J and BALB/cJ mice demonstrated large, nonhealing cutaneous lesions. In addition, BALB/cJ developed metastatic lesions on the extremities which progressively increased in size. A11 BALB/cJ and SWR/J mice died by 7 1/2 months of infection. The BALB/cJ female x C57BL/6J male F1 hybrid behaved in an intermediate fashion showing a slower expansion of cutaneous ulcers and a delayed development of metastatic foci, however, the infection ultimately proved fatal. The F2 generation could be separated into three distinct groups:resistant, intermediate, and susceptible mice with a lesion size distribution pattern in conformity with a 1:2:1 ratio. Male/female susceptibility differences were not noted. These data indicated that development of acquired resistance may be under the control of a single, autosomal gene. The gene did not appear to be H-2-, Ir-2-, or H-11-linked as is seen with Leishmania donovani infections.

Genetic analysis of renal function in mice. 1. Glomerular filtration rate and its correlation with body and kidney weight.

Investigation of 18 inbred and 6 F1 hybrid mouse strains has shown that the glomerular filtration rate, bodyweight and kidney weight showed strain- and sex-dependent differences. Covariance analysis showed stronger correlations (genetic and environmental) between glomerular filtration rate and bodyweight than between glomerular filtration rate and kidney weight. This was predominantly due to a high within-strain variation of kidney weight (56%) in male mice. Therefore an allometric regression was calculated between the 48 strain means of glomerular filtration rate (GFR) and bodyweight (BW): GFR = 0.036 x BW0.74. Thus the term BW0.74, a suitable correction term for comparing the heat production of different species, is also suitable for the correction of glomerular filtration rate within one species.

Regulation of T-cell-mediated lympholysis by the murine major histocompatibility complex. I. Preferential in vitro responses to trinitrophenyl-modified self K- and D-coded gene products in parental and F1 hybrid mouse strains.

Spleen cells from H-2b,k,d C57Bl/10 congenic mice were sensitized in vitro to trinitrobenzenesulfonate (TNBS)-modified autologous spleen cells. Cold target competition studies at the lytic phase demonstrated three distinct patterns of cytotoxic responsiveness: (a) H-2b spleen cells generated approximately equivalent CTL responses against Kb and Db modified self products, (b) H-2d spleen cells generated preferential responses against Dd modified self products, and (c) H-2k spleen cells generated cytotoxic responses which could only be detected against Kk self products in association with TNP. F1 spleen cells were sensitized against autologous TNBS-treated cells. The results showed that, although H-2b parental cells generated approximately equivalent Kb-TNP- and Db-TNP-specific CTL, the presence of the H-2b haplotype did not result in the generation of (a) Dk-TNP CTL response by (H-2b x H-2k) spleen cells, nor (b) a Db CTL response by (H-2b x H-2a) F1 spleen cells. Additionally, (H-2d x H-2k) F1 cells failed to generate detectable Dd-TNP-specific CTL, although H-2d parental cells generated D-regional-specific CTL. The findings demonstrated that these F1 response patterns paralleled those of the H-2k and H-2a parents, i.e. weak or no D-region TNP-specific CTL were induced. Because (H-2d x H-2a) F1 responders stimulated with H-2d TNBS-treated cells did generate good Dd TNP responses, the results illustrated that the presence of responder genes was not sufficient to result in a D-region TNP CML. It is suggested that the absence of Kk alleles on the stimulating population is necessary for the generation of D-region TNP CTL in these F1's. Mechanisms which could account for these response patterns in parental F1 mice are discussed including immunodominance, suppression, T-cell response , and Ir-gene defects.

Neoplasms of the Forestomach in Mice Ingesting Dihydrosafrole

The maximal tolerated doses of dihydrosafrole, safrole, and isosafrole were given by continuous oral administration, starting at the age of 7 days, to both sexes of two hybrid strains of mice - (C57BL/6 X C3HAnf)F1 and (C57BL/6 X AKR)F1. Hyperplasia and carcinomas of the forestomach were significantly increased in female mice of both strains and in male mice of the latter strain ingesting dihydrosafrole. By contrast, neoplasms of the forestomach were not increased in mice receiving safrole or isosafrole. Mice with neoplasms of the stomach generally did not have neoplasms of the liver.

Control of immunity in parental and F1 hybrid mouse strains to a spontaneously arising parental tumor. I. Correlation between in vitro and in vivo anti-tumor reactivity in responsive and unresponsive animals.

This study has investigated the in vivo and in vitro cellular immunity of the AKR/J, (AKR/J x C57BL/6)F1 and (AKR/J x DBA/2)F1 mouse strains to a spontaneously arising AKR/J tumor. The study concludes that: 1) there is an excellent correlation between the growth of the tumor in vivo, and the ability of spleen cells from the respective strains to generate both primary and secondary cell-mediated cytotoxic responses in vitro; and 2) one F1 host can be considered a responder against this tumor, whereas the other F1 strains studied appears to be genetically nonresponsive. Possible mechanisms relating to the observed patterns of response are discussed.