Incidence Of Spontaneous Leukemia Research Articles

Effects of oral administration of Echinacea purpurea (American herb) on incidence of spontaneous leukemia caused by recombinant leukemia viruses in AKR/J mice.

Four-week-old female AKR/J mice were given oral doses of powdered leaves from Echinacea purpurea three times weekly for 8 weeks (7.5 mg/mouse/week): controls received phosphate-buffered saline. Mean survival age of experimental AKR/J mice treated with the E. purpurea preparation was significantly prolonged and enlargement of thymic lymphoma in experimental mice was significantly suppressed compared with controls. In normal 3-week-old female AKR/J mice, mortality from thymic lymphoma was delayed markedly after injection into the thymus of cell-free extract of thymus from the experimental 28-week-old female AKR/J mice that received the oral E. purpurea preparation was injected directly into the thymus. Proliferation of endogenous recombinant murine leukemia viruses (MuLV) in the thymus was markedly inhibited after the first oral administration of the E. purpurea preparation as compared with untreated controls (final age, 28 weeks). Production of endogenous interferon (IFN)-gamma in AKR/J mice was also effectively augmented by the oral treatment with the E. purpurea preparation, however, the production of other cytokines such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-12 was minimal. These results suggest that this suppressive effects on spontaneously occurring leukemia caused by endogenous recombinant MuLV in female AKR/J mice may depend on enhancement of nonspecific immune or cellular immune systems (or of both) by the E. purpurea preparation.

Inhibition of the development of radiation-induced leukemia in mice by reduction of food intake.

We have reported previously that the incidence of tumors induced in Sprague-Dawley rats by total-body gamma-ray irradiation can be considerably reduced by restriction of food intake [Gross, L. & Dreyfuss, Y. (1984) Proc. Natl. Acad. Sci. USA 81, 7596-7598]. In experiments reported here we investigated the influence of reduced food intake on the development of radiation-induced leukemia in C3H(f) mice. The incidence of spontaneous leukemia in mice of this strain does not exceed 0.5%, but it can be considerably increased by total-body x-irradiation. In our study, two groups of C3H(f) mice were submitted to fractionated total-body gamma-irradiation (150 rads, five times at weekly intervals; 1 rad = 0.01 gray). The first group received a full ad lib diet (4.5-5.4 g of Purina Rodent Lab Chow pellets per day, each). In this group 31 out of 58 females (53.4%) and 24 out of 50 males (48%) developed leukemia at an average age of 8 months. In the second group, consisting of sisters and brothers of the first group, and submitted to the same gamma-irradiation but receiving a restricted diet (2 g of Purina Lab Chow pellets each, followed by 3 g on alternate days), only 2 out of 55 females (3.6%), and 1 out of 36 males (2.8%), developed leukemia at an average age of 9 and 12 months, respectively. Leukemia in both groups was predominantly of the lymphatic or lymphoblastic form, the leukemic cells infiltrating most organs, particularly the thymus, mesenteric and peripheral lymph nodes, spleen, liver, kidneys, and bone marrow; in most instances the peripheral blood was also leukemic.

Differences in Activity of <italic>N</italic><sup>2</sup> -Guanine tRNA Methyltransferase II Among Several Inbred Strains of Mice<xref ref-type="fn" rid="FN2">2</xref>

The tRNA methyltransferase activities of C57BL/6J, C57L/J, C58/J, AKR/J, and C3H/HeJ inbred mice were studied with the use of various amino acid-specific Escherichia coli tRNA's as substrates. Mice from two strains with high incidence of spontaneous leukemia (AKR/J and C58/J) exhibited levels of liver N2-guanine tRNA methyltransferase II (N2-MeGII) activity that were double those of two strains of mice with low incidence of spontaneous leukemia (C57BL/6J and C57L/J). Activities of liver and kidney N2-MeGII of the high spontaneous hepatoma strain C3H/HeJ were also found to be twice as high as those of C57BL/6J mice. The activities of other tRNA base-specific liver tRNA methyltransferases were very similar in all strains studied. The N2-MeGII activity of the F1 progeny of a cross between C57BL/6J and C3H/HeJ showed levels of activity intermediate to those of the parental strains. Activities of liver N2-MeGII of two inbred strains of mice that differ in their H-2 haplotype (C57BL/10SnJ and the congenic strain B10.BR/SgSnJ) were also compared. Both C57BL/10SnJ and B10.BR/SgSnJ strains exhibited low levels of liver N2-MeGII activity, indicating that H-2 does not directly control the activity of this enzyme.

Prevention of spontaneous leukemia in mice by oncornavirus immunization

C57L, NIH, and SWR mice were immunized with inactivated Gross leukemia virus (GLV) and then mated with AKR males. Their F1 offspring were then immunized with the murine sarcoma virus pseudotype of GLV, MSV(GLV). The concentrations of infectious ecotropic AKR virus in tail extracts of immunized mice were 100- to 1,000-fold lower than in non-immunized controls when tested at 30--40 days of age. Although viral titers increased slightly with time, the titers remained at least one log10 lower in the immunized mice than in non-immunized F1 control mice at all times tested. The reduction in the level of expression of endogenous ecotropic virus showed a highly significant positive correlation with the reduction in incidence of spontaneous leukemia in these mice. These data thus show that successful immunoprevention of leukemia in mice can be achieved with viral vaccines.

Ability of animals to give a humoral immune response and its effect on development of experimental leukemias

Experiments on AKR and C57BL mice of different ages, using experimental models of transplantable Gross (first generation), Pujman, and spontaneous leukemia of AKR mice, showed that the ability of mice to produce humoral antibodies is inversely proportional to their susceptibility to inoculation of syngeneic leukemic cells and also to the incidence of spontaneous leukemia. The difference in ability to form an immune response to heterologous antigen were due to the physiological processes taking place in the aging organism. The results indicate that a failure of one component of immunity does not necessarily lead to an increased risk of tumor development in vivo.

Correlation of early murine leukemia virus titer and H-2 type with spontaneous leukemia in mice of the BALB/c times AKR cross: a genetic analysis.

Tissue extracts from 6-wk old mice of the AKR strain (H-K) show high levels of infectious murine leukemia virus, and these mice show a near 100% incidence of spontaneous leukemia. In F1 mice of the cross, BALB/c times AKR (H-2K/H-2K), both the occurrence of virus and the incidence of spontaneous leukemia are suppressed to very low values, due largely to the presence of the FV-1b allele inherited from the BALB/c parent. Mice of the (BALB/c times AKR) F-1 times AKR backcross generation were observed for possible correlations between virus expressions at 6 wk of age, H-2 type and leukemia incidence. H-2 type showed at most a weak influence on the occurrence of infectious virus, but there was a very strong correlation between the level of virus expression and the occurrence of leukemia and a strong correlation between H-2 type and leukemia. In addition, there was a highly significant nonrandom distribution of virus-negative mice among the backcross litters, suggesting a maternal effect on virus expression.

Virus Particles in Placenta and Uterus of RIII/Dm Strain Mice

Recent observation of type C virus particle synthesis in placenta of baboons and in human placenta has focused attention on the possible role of that organ in vertical transmission of oncogenic RNA viruses. Distribution of type C (murine leukemia) and type B (mouse mammary tumor) virus particles in some tissues of mice of strain RIII, a strain with high incidence of spontaneous mammary tumors (70%) and low incidence of spontaneous leukemia (3%) has been extensively studied by electron microscopy. However, their distribution in placenta and uterus of RIII mice has not been investigated so far.

Formation of virus-like particles by bone cells in mice with a high incidence of spontaneous leukemia.

Bone samples from potentially leukemic and leukemic mice revealed numerous 90-to 110-nanometer particles morphologically identical to murine leukemia virus. Particles were observed budding from plasma membranes of osteocytes and osteoblasts but were most numerous in osteocyte lacunae. Particles were not observed in bone samples from mice which rarely develop leukemia.

Distribution of virus-like particles in the lymphatic tissues of "nonleukemic" CFW-w conventional mice.

SummaryA study was made on the “non-leukemic” conventional CFWW mice which show a 29% incidence of spontaneous leukemia by 24 months of age. An estimate on the presence of virus particles in the thymus showed 61% with C type particles and 28% with A2 particles. In addition, 22% of the spleens and 17% of the lymph nodes examined contained C type particles. The C type particles in the thymus were associated with epthelial cells while the A2 particles were within lymphocytes. This particle concentration within certain cell types, as it may relate to sampling error, was discussed. The implication of the thymus as a source of virus was discussed, including the possible role of the thymic blood barrier and epithelial cells in the “release” of particles to other lymphatic tissues.

Effect of BCG infection on leukemia and polyoma in mice and hamsters.

SummaryIn Ak mice inoculated with live BCG and submitted to isologous transplantation of leukemic tissue, body weight was maintained longer, partial regression of local implanted tumors was observed, development of leukemia was delayed and survival prolonged, as compared with controls without BCG infection. In Ak mice similarly treated with BCG, the incidence of spontaneous leukemia was decreased and death was significantly retarded. In hamsters inoculated with live BCG and subsequently with polyoma virus, development of polyoma was delayed and survival considerably prolonged.

Expositionsdosen des Knochenmarks bei einigen modernen röntgenologischen Untersuchungsmethoden des Herzkreislaufapparates

Measurements were made of the radiation dose received by the bone marrow during cardiac catheterization with prolonged screening and angiocardiograms with biplane apparatus. For this purpose a phantom resembling a human body and containing bones inside scattering material was employed. From the data obtained, the average dose and the integral dose received by the bone marrow were calculated. It was found that during cardiac catheterization without correct protection procedure the average dose received by active bone marrow exceeded that which is said to double the incidence of spontaneous leukemia (which is, according to Court Brown, 50 r). (auth)

Parents’ Age Unrelated to Leucosis in Progeny

Coles (1955) stated that “birds in their hen year failed to transmit resistance (to leucosis) because of incomplete ability to do so with increasing age” and that “a parent bird may increasingly fail with age to transmit genetic resistance to its offspring.”Age has no influence upon the genotype of an individual bird nor does it determine which genes are distributed to the functional gametes. Coles did not specify any mechanism by which age of the dam might influence resistance of her progeny, and the data given in support of his theory were scarcely conclusive.However, since in mice a non-chromosomal influence of age of dam on the incidence of spontaneous leukemia in her progeny is known (MacDowell, Potter and Taylor, 1945), it seemed desirable to examined our records for any evidence that might support Coles’s theory.From the records of our White Leghorns for the six years, 1949 to …

Pathogenic Properties, and "Vertical" Transmission of the Mouse Leukemia Agent.

1. When centrifugated extracts of Ak mouse leukemia were inoculated into 16 suckling C3H(f) infant mice less than 12 hours old, “spontaneous” leukemia developed in 8 of them at 81/2 to 11 months, and in 5 mice at 14 to 18 months of age. 2. When the centrifugated leukemic extracts were inoculated into 20 C3H(f) infant mice 3 to 6 days old, “spontaneous” leukemia developed in 10 of them, but not before they were 18 months of age. 3. Filtered (Seitz) leukemic extracts were inoculated, in 2 experiments, into 7 C3H(f) infant mice 8 days old, and 2 of them developed leukemia at 23 and 27 months respectively. In 5 additional experiments, leukemic filtrates were inoculated into 25 C3H(f) infant mice less than 12 hours old, and 7 of them developed “spontaneous” leukemia at 61/2 to 9 months of age. These results suggest that the Ak mouse leukemia agent is filterable. 4. In 5 experiments, suckling infant C3H or C3H(f) mice were inoculated with either centrifugated leukemic extracts, leukemic cell suspensions, or with normal Ak-embryo-cell suspensions. After the inoculated infant mice have grown up and reached sexual maturity, they were mated, Of the 10 inoculated parents, 7 eventually developed “spontaneous” leukemia at 9 to 19 months of age. Of the 27 untreated offspring, 13, or 48%, have thus far developed “spontaneous” leukemia at 14 to 20 months of age. The results of these experiments suggest that the mouse leukemia agent is transmitted from parents to their offspring. The transmission of the agent occurs most probably directly through the embryos(2,4). 5. The incidence of spontaneous leukemia among the untreated males and females of the C3H or C3H(f) colonies of mice in our laboratory has been, during the past several years, less than 0.07%.