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At least 19 recordsLinked to original sources
PubMed1979

The murine Ah locus: in utero toxicity and teratogenesis associated with genetic differences in benzo[a]pyrene metabolism.

Benzo[a]pyrene, at dose between 50 and 300 mg per kg body weight given at Day 7 or 10 of gestation, causes in utero toxicity and teratogenicity more so in genetically "responsive" C57BL/6 than in "nonresponsive" AKR inbred mice. With the use of AKR X (C57BL/6) (AKR)F1 and (C57BL/6) (AKR)F1 X AKR backcrosses, it was shown that allelic differences at the Ah locus in the fetus can be correlated with dysmorphogenesis. If the mother is nonresponsive (Ahd/Ahd), the Ahb/Ahd genotype in the fetus is associated with more stillborns and resorptions, decreased fetal weight, increased congenital anomalies, and enhanced P1-450-mediated covalent binding of BP metabolites to fetal protein and DNA, when compared with the Ahd/Ahd genotype in the fetus from the same uterus. If the mother is responsive (Ahb/Ahd), however, none of these parameters can be distinguished between Ahb/Ahd and Ahd/Ahd individuals in the same uterus, presumably because enhanced BP metabolism in maternal tissues and placenta cancels out these differences between individual fetuses. Of particular interest in our study is the fact that the mother and the father both must be of a particular genotype before differences in teratogenesis among fetuses (due to their genotype) will be expressed. These data might provide an example in attempting to explain clinically why only one child is affected with an apparent "drug-induced syndrome" although the mother has taken the same dose of the particular drug during each of numerous pregnancies.

Abnormalities, Drug-Induced↗
PubMed1979

[Use of inhibition by metyrapone in a "mutual depletion system" for evaluation of active centres of various arylhydrocarbon hydroxylases].

It was shown that metyrapone, the inhibitor of arylhydrocarbonhydroxylase, taken at concentrations equimolar to that of cytochrome P-450 non-competitively inhibits the hydroxylation of 3,4-benzpyrene in the liver microsomes of inbred mice of the C57BL/6 and AKR strains. In a given "mutual depletion inhibition system" the concentration of the catalytically active centres of microsomal cytochrome (Ecac), their turnover number (TNcac) and "true" dissociation constant of the enzyme-inhibitor complex were determined in the control and 3-methylcholanthrenetreated mice of both strains. The increased rate of 3,4-benzpyrene hydroxylation in the liver of 3-methylcholanthrene-induced "sensitive" C57BL/6 mice is determined by the increase of Ecac (and, in a lesser degree, of TNcac) per molecule of cytochrome P-448. In the liver microsomes of "induction-resistant" AKR mice an injection of 3-methylcholanthrene results in a slight increase of Ecac and a simultaneous decrease of TNcac. It was assumed that contrary to the present-day concepts, an aberrant microsomal hemoprotein with a genetically determined low molecular activity is synthesized in mice of "resistant" AKR strain.

Animals↗
PubMedDate not supplied

[Further study of the hormonal regulation of natural immunity to weak transplantation antigens in inbred mice].

Blood plasma corticosterone level and the extent of immunological reaction to sex-antigen of skin transplant in inbred mice CBA, C57Bl/6, F1 (CBA X 57Bl/6), C3H, AKR was compared. Mice CBA had a high blood plasma corticosterone level and no immunological reaction to sex-antigen. A lower blood corticosterone level and the presence of reaction to sex-antigen was characteristic of mice C57Bl/6, AKR, C3H, F1(CBA X C57Bl/6). The number of endogenous colonies in the spleen of mice CBA was less than in mice C57Bl/6. Mice CBA had a narrow cortical thymus layer in comparison with the wide thymus cortex of mice AKR and C57Bl/6. Adrenalectomy of mice CBA caused a sharp widening of the thymus cortex.

Adrenalectomy↗
PubMed1978

[Morphological and functional interrelationships of the thymus and adrenals in inbred mice].

The authors carried out morphological examination of the thymus, adrenal glands and the spleen in CBA, C57BL/6, AKR mice and studied the immunological reactivity of mice to sex antigen of the skin transplant with the determination of the blood plasma corticosterone level. In comparison with C57BL/6 and AKR mice, CBA mice displayed a narrow cortical layer in the thymus, wide thymus-dependent zones in the spleen, a high corticosterone level, and the absence of any reaction to the sex antigen of the skin transplant. Adrenalectomy in CBA mice led to a sharp dilatation of the thymus cortex, the appearance of numerous lymph follicles in the spleen and development of an immunological reaction to sex antigen of the skin transplant. Atrophy of the cortical layer of the adrenal glands witha sharp reduction of subanophilic lipids was noted in CBA B-mice.

Adrenal Glands↗
PubMed1977

C-type virus protein p30 in blood from inbred mice correlates with their later incidence of leukemia.

The major core protein, p30, of mouse C-type viruses was quantitated radioimmunologically in lymphoid organs and blood from inbred strains of mice. The concentration of p30 in thymus and spleen had a weak and moderate correlation, respectively, to leukemia frequency. In contrast, the concentration of p30 in blood from mice with a high incidence of leukemia (strains AKR and C58) was 100-fold increased at 2 months of age compared with 10 strains with a low incidence of the disease. The SJL mice, which have a high incidence of reticulum cell neoplasms, showed generally elevated, but variable, values. The high concentration in AKR blood developed during the first weeks of life. Approximately one-third of the DBA/2 mice had elevated levels after 4 to 5 months, whereas the values from mice of the 129 strain were low irrespective in their age. The major part of p30 appeared to be associated with the erythrocytes. The concentration of p30 in the blood seems to reflect the presence of replicating virus in mice. It identifies among the inbred strains a high leukemia group one-half year prior to disease.

Age Factors↗
PubMed1977

[Detection of antigens of endogenous viruses of the C-type during mouse development].

Embryos of the 12th-20th day of gestation, newborn and adult AKR and BALB/c mice were investigated for the presence of mouse C-type virus major structural p30 protein (gs-1) and Gross leukemia virus type-specific antigen AGLV) by means of radioimmunodiffusion with test systems. The p30 protein was distinctly determined from the 12th day of intrauterine development in both mouse lines; it persisted in the embryo tissues until birth and was detectable also in the AKR and BALB/c mouse tissues from the first days of postnatal development and during the whole life. AGLV was not revealed in BALB/c and AKR embryos and in adult BALB/c mice; however it was found in the AKR newborn mice since the 1st-2nd day after birth. Basing on these data a conclusion was drawn that p30 protein and AGLV were expressed independently according to the radioimmuno-diffusion method sensitivity.

AKR murine leukemia virus↗
PubMed1975

Qualitative and quantitative studies of AKR-type murine leukemia virus sequences in mouse DNA.

Utilizing a single-stranded [3H]DNA probe highly representative of AKR viral 70S RNA, we have performed association kinetics experiments with cellular DNA in vast excess from 3 high-, 5 low- and 4 non-virus-yielding mouse strains. Our hybridization studies indicate that in the strains so far tested, the complete genome of the AKR-type MLV is present in the DNA of the embryos of both high- and low-virus-yielding mouse strains, while DNA of non-virus strains contains only a part of the genome. Furthermore, at least two populations of virus-specific DNA sequences can be identified (more abundant and less abundant species) according to their rate of association. Low-virus-yielding mouse strains contain a smaller number (1-2 copies) of the less abundant species, and thus a lower number of complete viral genome than do high-virus strains (3-4 copies). Non-virus-yielding strains are lacking these less abundant sequences in their genome. DNA from wild Mus musculus also contained viral sequences, the sample tested showing association kinetics identical to the non-virus-producing strains. Thus there is a good correlation between completeness of the AKR-type MLV genome in cellular DNA and the capacity of the cells to release AKR-type MLV. Mice of a non-virus-yielding strain made partially congenic for the AKR virus-inducing locus Akv-1 contained the complete virus genome, confirming that this locus consists of structural genes of the virus.

AKR murine leukemia virus↗
PubMed1975

In vivo interactions between murine leukemia and sarcoma viruses.

Experiments have been performed with the aim of elucidating the nature and the extent of the in vivo interactions between murine leukemia viruses (MuLVs) and murine sarcoma virus (MSV). BALB/c and CBA mice, injected neonatally with Graffi or passage A Gross viruses (MuLV-Gi, MuLV-G), have been inoculated as young adults with murine sarcoma virus, Moloney strain (MSV-M). A higher percentage of nonregressing sarcomas appeared in these animals, sometimes accompanied simultaneously by leukemia. The immune reactivity of mice receiving MuLV-Gi at birth was found to be significantly depressed when evaluated by the hemolytic palque-forming cell (PFC) technique. However, in mice infected with MuLV-Gi and MSV-M the number of PFC ranged within the control values or slightly increased. The potentiation of MSV-M oncogenicity following infection with MuLV was studied in a more natural situation. Adult AKR mice, known to release endogenous MuLV continuously, were injected with MSV-M. The incidence of induced sarcomas was similar to that observed in control BALB/c mice inoculated with MSV-M. Moreover, tumors developed with a very long latent period. On the other hand, the great majority of tumors showed no regression and ultimately killed the host. Additional experiments, making use of immunologic manipulation of the host and Fl hybrids, suggest that the relative resistance to MSV-M oncogenesis in AKR mice is influenced by genetic and immunologic factors. MSV recovered from MSV-M-induced tumors in AKR and C58 mice was typed by highly specific mouse antisera. The results clearly showed that formation of a new MSV pseudotype occurred in vivo, the endogenous Gross virus acting as helper.

AKR murine leukemia virus↗
PubMed1975

Alien histocompatibility determinants on the cell surface of sarcomas induced by methylcholanthrene. I. In vivo studies.

Groups of BALB/c mice were immunized to normal tissues (skin and/or liver plus kidney) of C3Hf, C57Bl/6, DBA/2 and AKR strains and challenged with either of two syngeneic 3-methylcholanthrene-induced immunogenic sarcomas, ST2 and TZ15, or with a "spontaneous" non-immunogenic BALB/c sarcoma, B2. It was found that anti-C3Hf and anti-DBA/2 immune mice were significantly protected against the growth of ST2, whereas anti-AKR immune mice rejected TZ15; no protection was elicited by immunizing with normal tissues of any strain against B2, which lacked individual tumor-associated transplantation antigens (TATA). The reciprocal experiment, i.e. the immunization of BALB/c mice with tumor cells and challenge with skin grafts of different strains, was also carried out with ST2 and TZ15. Accelerated rejection of all the various allogeneic skins was observed in anti-ST2 immune mice and of AKR and C3Hf skin in anti-TZ15 immune animals. In addition the Winn test demonstrated that lymph-node cells of BALB/c mice immune to C3Hf or DBA/2 tissues were specifically inhibitory for ST2, and that lymph-node cells immune to AKR tissues protected against TZ15. In a further experiment both ST2 and TZ15 tumors were left to grow in (C3Hf X BALB/c)F1, (C57Bl/6 X BALB/c)F1, (BALB/c X DBA/2)F1 and (BALB/c X AKR)F1 mice; the tumors were then excised and the "immune" mice challenged with the related tumor to measure their immune response in comparison with that elicited by the same procedure in BALB/c mice. ST2 was highly immunogenic in syngeneic BALB/c mice and in all the hybrid combinations except (C3Hf X BALB/c)F1 mice, where it completely lost its immunogenicity; TZ15 showed a certain loss of immunogenic strength in (BALB/c X AKR)F1 hybrids. It was concluded that TATA of ST2 contain antigenic determinants expressed on the normal cells of C3Hf and DBA/2 strains, and that TATA of TZ15 are likely to share antigens with AKR normal tissues.

Animals↗
PubMed1977

Isolation and comparison of murine leukemia virus-related glycoproteins from AKR and New Zealand mice.

The major glycoprotein (gp70) of murine leukemia virus occurs free of virus in the serum and body fluids of certain strains of mice. These glycoproteins were isolated from New Zealand Black mouse (NZB) ascites fluid and from AKR and New Zealand White mouse (NZW) serum by immunoaffinity chromatography and were compared by immunological tests and peptide mapping. Glycoproteins gp70-NZB and gp70-NZW were indistinguishable by all criteria tested and were more closely related to gp70 from Moloney leukemia virus than was gp70-AKR.

Animals↗
PubMed1976

[The type specific antigen of Gross leukemia virus in tumors and normal tissues and its identification by immunodiffusion methods].

A monospecific antiserum for type-specific antigen of Gross virus (AGLV) was obtained. Tumours of different origin were studied with this monospecific antiserum in the gel-diffusion test. AGLV was revealed in spontaneous kidney tumour of CC57BR mice, and in chemically (carcinogen)- induced tumours of mice. These findings suggest activation of MuLV viral genom in low-leukemic strains of mice.

9,10-Dimethyl-1,2-benzanthracene↗