Resistance to murine leukemia in mice rejecting syngeneic somatic hybrid cells.

(A/J X C3H/HeJ) F1 mice reject somatic cell hybrids of ASL-1 cells (A origin) and LM(TK)- cells (C3H origin), but die from leukemia within 10 days after the inoculation of approximately 10(6) viable ASL-1 cells. Mice rejecting hybrid cells survive for prolonged periods after challenge with otherwise lethal numbers of ASL-1 cells. The hybrid cells, rejected by syngeneic F1 recipients, retained their oncogenic potential as determined by the appearance and progressive growth of tumors in immunologically deficient nu/nu mice injected with the cells. Similar results were obtained using hybrids of a radiation-induced cell line (RADA-1), maintained by serial transfer in strain A mice and LM(TK)- cells. Syngeneic mice injected with RADA-1 X LM(TK)- cells failed to form tumors. Mice rejecting RADA-1 X LM(TK)- hybrid cells survived for prolonged periods after challenge with otherwise lethal numbers of RADA-1 cells.     

Differences in antibody production against mouse hepatitis virus (MHV) among mouse strains

Several strains of mice were examined for antibody production after intranasal inoculation with a low virulence strain of mouse hepatitis virus (MHV), MHV-NuU. C57BL/6N mice were shown to be high responders in the production of complement fixing (CF) antibody as compared to C3H/HeN, BALB/c-AnN, DBA/2N mice. F1 hybrids B6C3 and BDF1 from C57BL/6N mice, showed CF antibody responses as high as C57BL/6N, suggesting that high responsiveness is genetically controlled. All these mouse strains were able to produce high titred neutralizing antibody to MHV.     

Suppressor T cells arising in mice undergoing a graft-vs-host response.

We investigated the ability of mice to generate antibody-forming cells when undergoing a graft-vs-host reaction. (C57BL/6 X DBA/2)F1 mice (BDF1) injected with C57BL/6 spleen cells generated suppressor T cells which inhibit antibody synthesis by BDF1 spleen cells in vitro. These T cells arose from the donor inoculum. They differ from helper T cells in size and they act directly on antigen reactive B cells. The suppressor T cells were specifically directed against components of the H-2 region of the reciprocal parental strain (DBA/2 = H-2d) in the hybrid F1 mouse.     

Food restriction-like effects of dietary dehydroepiandrosterone. Hypothalamic neurotransmitters and metabolites in male C57BL/6 and (C57BL/6 x DBA/2)F1 mice

Dehydroepiandrosterone (DHEA) is a precursor of sex hormones in mammals. Dietary DHEA serves to prevent or inhibit various diseases and also lengthens life spans of animals. Moreover, dietary DHEA inhibits food intake in certain strains of mice. We administered DHEA (0.45% w/w of food) to C57BL/6 (B6) and (B6 x DBA/2)F1 (BDF1) mice for 5 weeks. Food intake was inhibited in both strains of mice during the first week. Thereafter, B6, but not BDF1, mice consumed less food. Because hypothalamic serotonin and/or dopamine regulate appetite, satiety and other behaviors, the hypothesis tested was that hypothalamic concentration of serotonin, dopamine and/or their metabolites are affected differentially in B6 and BDF1 mice fed DHEA. In another study, mice were fed the AIN-76A diet with or without DHEA for 1 and 7 days or were pair-fed to DHEA-fed mice for 7 days. On Day 1 of DHEA feeding (acute effects) hypothalamic levels of serotonin, dopamine, and metabolites were unchanged in B6 mice, but levels of dopamine were increased and levels of dopamine metabolites were decreased in BDF1 mice. On Day 7 of DHEA feeding, levels of serotonin were increased in BDF1 but not B6 mice. On Day 7 of pair-feeding there were decreased levels of hypothalamic dopamine metabolites in BDF1 but not B6 mice. Paraventricular nuclei of BDF1 mice had decreased levels of serotonin but not of dopamine in all groups. Serum levels of DHEA and its metabolite, 5-androstene-3beta,17beta-diol, correlated significantly only with serotonin concentrations in BDF1 mice. The salient findings of these experiments are that DHEA inhibits food intake to a greater extent in B6 than in BDF1 mice. However, alterations of hypothalamic neurotransmitters were greater in BDF1 than in B6 mice. Because BDF1 and B6 mice share B6 genes, relevant gene(s) derived from DBA/2 mice might mediate the different responses detected.     

Comparison of tetraploid blastocyst microinjection of outbred Crl:CD1(ICR), hybrid B6D2F1/Tac, and inbred C57BL/6NTac embryos for generation of mice derived from embryonic stem cells

Embryo electrofusion and tetraploid blastocyst microinjection is a modification of the traditional embryonic stem cell (ES cell)-based method to generate targeted mutant mice. Viability of tetraploid embryos is reportedly lower than with diploid embryos, with considerable interstrain variation. Here we assessed fetus and pup viability after ES cell microinjection of tetraploid blastocysts derived from outbred, hybrid, and inbred mice. Two-cell mouse embryos (C57BL/6NTac [B6], n = 788; B6D2F1/Tac [BDF1], n = 1871; Crl:CD1(ICR) [CD1], n = 1308) were electrofused; most resultant tetraploid blastocysts were injected with ES cells and surgically transferred into pseudopregnant recipient mice. Reproductive tracts were examined at midgestation for embryologic studies using B6 and BDF1 blastocysts; implantation sites and viable fetuses were counted. Pregnancies were carried to term for studies of targeted mutant mice using BDF1 and CD1 blastocysts, and pup yield was evaluated. Electrofusion rates of 2-cell embryos did not differ among B6, BDF1, and CD1 mice (overall mean, 92.8% +/- 5.4%). For embryologic studies, 244 B6 blastocysts were surgically transferred and 1 fetus was viable (0.41%), compared with 644 BDF1 blastocysts surgically transferred and 88 viable fetuses (13.7%). For targeted mutant mouse studies, 259 BDF1 blastocysts were surgically transferred yielding 10 pups (3.9%); 569 CD1 blastocysts yielded 44 pups (7.7%).     

Friend leukemia virus infection enhances DNA damage-induced apoptosis of hematopoietic cells,causing lethal anemia in C3H hosts

Exposure of hematopoietic progenitors to gamma irradiation induces p53-dependent apoptosis. However, host responses to DNA damage are not uniform and can be modified by various factors. Here, we report that a split low-dose total-body irradiation (TBI) (1.5 Gy twice) to the host causes prominent apoptosis in bone marrow cells of Friend leukemia virus (FLV)-infected C3H mice but not in those of FLV-infected DBA mice. In C3H mice, the apoptosis occurs rapidly and progressively in erythroid cells, leading to lethal host anemia, although treatment with FLV alone or TBI alone induced minimal apoptosis in bone marrow cells. A marked accumulation of P53 protein was demonstrated in bone marrow cells from FLV-infected C3H mice 12 h after treatment with TBI. Although a similar accumulation of P53 was also observed in bone marrow cells from FLV-infected DBA mice treated with TBI, the amount appeared to be parallel to that of mice treated with TBI alone and was much lower than that of FLV- plus TBI-treated C3H mice. To determine the association of p53 with the prominent enhancement of apoptosis in FLV- plus TBI-treated C3H mice, p53 knockout mice of the C3H background (C3H p53(-/-)) were infected with FLV and treated with TBI. As expected, p53 knockout mice exhibited a very low frequency of apoptosis in the bone marrow after treatment with FLV plus TBI. Further, C3H p53(-/-) --> C3H p53(+/+) bone marrow chimeric mice treated with FLV plus TBI survived even longer than the chimeras treated with FLV alone. These findings indicate that infection with FLV strongly enhances radiation-induced apoptotic cell death of hematopoietic cells in host animals and that the apoptosis occurs through a p53-associated signaling pathway, although the response was not uniform in different host strains.     

Effects of benzo(a)pyrene on Friend viral leukemogenesis in B10SJF1 mice

A single intraperitoneal injection of benzo(a)pyrene (BP) given 1, 2, or 3 days before an ip injection of Friend leukemia virus (FLV) significantly increased the leukemogenic effect of the virus in B10SJF1 mice. These hybrids are the offspring of C57BL/10 females and SJL/J males and are highly resistant to FLV leukemogenesis when the virus is injected alone.     

Use of silica to identify host mechanisms involved in suppression of established Friend virus leukemia.

Silica, an agent predominantly toxic for macrophages, inoculated i.v. to Friend leukemia virus (FLV)-infected mice, blocks the FLV-leukemosuppressive effects of chlorite-oxidized oxyamylose (COAM)-statolon treatment. FLV-infected, COAM-statolon-treated mice that have received silica and have failed to suppress FLV leukemia produced normal amounts of interferon, but did not make antibodies cytotoxic for FLV leukemic cells. Transfer of untreated spleen cells, splenic T cells, or thymocytes from mice with suppressed FLV erythroleukemia to FLV-infected mice treated with silica and COAM-statolon restores the humoral immune response to FLV antigens and results in leukemosuppression. Thus, T lymphocytes from mice with suppressed erythroleukemia participate in FLV leukemosuppression either directly as effector cells, or indirectly as helper cell in the production of antibodies to FLV antigens.     

Interleukin-2 production during murine infection by Leishmania mexicana amazonensis

Highly susceptible BALB/c mice, resistant C57B1/6 and their F1 progeny (BDF1) were infected subcutaneously in the foot pad with Leishmania mexicana amazonensis. At various times after infection, spleen or draining popliteal lymph node cells were assayed for their capacity to generate Interleukin-2 (I1-2) by Concanavalin A (ConA) stimulation. In both BALB/c and C57B1/6 strains there was a transient increase in their capacity to produce I1-2, from the 3rd to the 10th week post-infection. Return to pre-infection levels occurred between 13th to 16th week post-infection in all three strains. BALB/c mice always produced higher titers of I1-2 than C57B1/6, but such differences were statistically significant only at 3 and 10 weeks post-infection. BDF1 mice had titers similar to those observed in BALB/c mice. I1-2 production by ConA-stimulated lymph node cells was lower as compared to the spleen, but with a similar pattern among the three mice strains. Our data show that susceptibility to infection by L. mexicana amazonensis is not associated with deficient ConA-stimulated I1-2 production.     

Differential Requirements of Cellular and Humoral Immune Responses for Fv2-Associated Resistance to Erythroleukemia and for Regulation of Retrovirus-Induced Myeloid Leukemia Development

To assess the possible contribution of host immune responses to the exertion of Fv2-associated resistance to Friend virus (FV)-induced disease development, we inoculated C57BL/6 (B6) mice that lacked various subsets of lymphocytes with FV containing no lactate dehydrogenase-elevating virus. Fv2^r B6 mice lacking CD4⁺ T cells developed early polycythemia and fatal erythroleukemia, while B6 mice lacking CD8⁺ T cells remained resistant. Erythroid progenitor cells infected with spleen focus-forming virus (SFFV) were eliminated, and no polycythemia was observed in B cell-deficient B6 mice, but they later developed myeloid leukemia associated with oligoclonal integration of ecotropic Friend murine leukemia virus. Additional depletion of natural killer and/or CD8⁺ T cells from B cell-deficient B6 mice resulted in the expansion of SFFV proviruses and the development of polycythemia, indicating that SFFV-infected erythroid cells are not only restricted in their growth but are actively eliminated in Fv2^r mice through cellular immune responses.     

Specific inhibition of hybrid resistance in F1 hybrid mice pretreated with parent strain spleen cells. I. Induction of a nylon-adherent, Thy-1+Lyt-1+2- suppressor cell

Hybrid resistance, which is observed in certain strain combinations when parent-strain bone marrow cells are grafted into lethally irradiated F1 hybrids, can be specifically overcome by the i.v. injection, 1 wk before the graft, of spleen cells syngeneic with the bone marrow graft. This phenomenon is due to a suppressor mechanism, induced in the spleen of the F1 hybrid by the injection of parent-strain spleen cells and mediated by a nylon-adherent Thy-1+Lyt-1+2- cell population of hybrid origin, because hybrid resistance can be inhibited by the transfer into a normal B6D2F1 of nylon-adherent Thy-1+Lyt-1+2- spleen cells from B6D2F1 mice pretreated with B6 spleen cells 1 wk earlier (B6-pretreated B6D2F1); spleen cells from B6-pretreated B6D2F1 mice not depleted of their nylon-adherent subpopulation cannot restore hybrid resistance when they are injected into a B6D2F1 rendered nonresistant by split-dose irradiation; and spleen cells from normal B6D2F1 mice cannot restore hybrid resistance when they are injected into B6-pretreated B6D2F1 hybrids. The suppressor cells specifically inhibit resistance against bone marrow cells syngeneic with the spleen cells used for pretreatment, because transfer of nylon-adherent B6-pretreated B6D2F1 spleen cells into a normal B6D2F1 does not enhance syngeneic B6D2F1 or parent-strain D2 bone marrow growth, and when injected into normal B6D2F1 hybrids, nylon-adherent spleen cells from B6D2F1 mice pretreated with D2 spleen cells 1 wk earlier (D2-pretreated B6D2F1) are not able to transfer the inhibition of hybrid resistance against B6 bone marrow cells. Moreover, the activity of the suppressor cells depends on the genetic environment of the hybrid host mice, because nylon-adherent B6-pretreated B6D2F1 spleen cells injected into normal B6C3F1 hybrids do not transfer an inhibition of hybrid resistance, and when injected into B6C3F1 hosts previously rendered nonresistant by split-dose irradiation, spleen cells from B6-pretreated B6D2F1 mice can, in contrast, transfer hybrid resistance.     

The use of cytotoxic T cells in the regulation of tumour growth in syngeneic mice

Summary Normal C57BL/6 (B6) spleen cells were cultured with syngeneic EL4 tumour cells, expanded in IL2-containing medium, and tested for anti-tumour activity in vitro and in vivo. The activated cells were highly cytotoxic for EL4 and to a lesser degree killed syngeneic B6 blasts and allogeneic (D2) P815 tumour cells. B6 or BDF1 mice that received these cultured cells by IP injection cleared ¹²⁵IUdR-labelled EL4 cells faster than untreated mice. However, this enhanced clearance was evident only 7–12 days after injection. Since the injected cells had a short half-life (<10% remaining after 48 h) the effect of these cells in vivo was most probably due to the activation of the host's immune system. Mice that received cultured cells survived significantly longer than untreated mice following a lethal dose of EL4 cells. Cultured cells were much more effective in prolonging survival when used in conjunction with cyclophosphamide (CY). In animals receiving either cultured cells with or without CY or CY alone tumour clearance was markedly enhanced 7–12 days after injection.When challenged with a small dose of EL4 tumour cells (1×10⁴ SC per mouse) three of ten B6 mice treated with B6 anti-EL4 cultured cells were able to survive indefinitely. The frequency of CTL precursors to EL4 from the spleen cells of these surviving animals was about five-fold higher than that of normal spleen cells. Furthermore, CTL derived from primed spleen cells were more specific for EL4 than those derived from normal spleen cells.Abbreviations B6 C57BL/6J - BDF1 (C57BL/6J×DBA/2J) F1 - ConA SN concanavalin A supernatant - CTL cytotoxic T lymphocytes - CTL-P cytotoxic T-lymphocyte precursors - CY cyclophosphamide - E/T effector-to-target ratio - IL2 interleukin 2 - IP intraperitoneal - IUdR iododeoxyuridine - IV intravenous - LPS lipopolysaccharide - MST mean survival time     

Expression of hemopoietic histocompatibility antigens on H-2-loss variants of F1 hybrid lymphoma cells: evidence consistent with trans gene regulation

H-2 heterozygous marrow stem cells, lymphoid progenitor cells, and leukemia/lymphoma cells do not express hemopoietic or hybrid histocompatibility (Hh) antigens, which are important transplantation antigens recognized during the rejection of normal or neoplastic hemopoietic cells. The Hh-1b determinant of the H-2b haplotype maps to the D region of H-2. We have tested the hypothesis that gene(s) at or near H-2D of the H-2d haplotype down-regulate the expression of Hh-1b in the trans configuration. We used Abelson leukemia virus-transformed pre-B lymphoma cells (ACCb) of BALB/c X BALB.B (H-2d X H-2b) origin, as well as variant lines of ACCb, which were selected for resistance to monoclonal anti-H-2 antibodies plus complement. B6D2F1 (H-2b X H-2d), C3B6F1 (H-2k X H-2b), or B6 (H-2b) mice were infused with inocula of 5 X 10(6) B6 bone marrow cells (BMC). Proliferation of donor-derived marrow cells was judged in terms of DNA synthesis by measuring the splenic incorporation of 5-iodo(125I)-2'-deoxyuridine (IUdR) 5 days after cell transfer. B6 BMC grew much better in B6 than in F1 hybrid host mice, an expression of "hybrid resistance". As observed previously, the injection of EL-4 (H-2b, Hh-1b) tumor cells prior to infusion of B6 (H-2b, Hh-1b) BMC enhanced the growth of B6 BMC in F1 hybrid mice. Therefore, this in vivo "cold target cell competition" type of assay can be used to detect the expression of Hh-1b antigens. Unlike EL-4 (H-2b) cells, hybrid resistance was not affected by prior infusion of (H-2b X H-2d) heterozygous ACCb cells. In contrast, three ACCb variant cell lines, H-2d-, Ld-Dd-, and Dd-, enhanced the growth of B6 BMC in F1 hosts. The ACCb H-2b- cell line did not affect hybrid resistance to B6 BMC. The loss of gene expression on the H-2d chromosome at or very near the H-2Dd locus is correlated with the appearance Hh-1b, as determined by the in vivo cold target competition assay. These results support the hypothesis that heterozygous cells possess trans-acting, dominant, down-regulatory genes mapping near H-2D that control the Hh-1 phenotype of lymphoid tumor cells.     

Genetic interactions in induction of endogenous murine leukemia virus from low leukemic mice

The frequency of ecotropic murine leukemia virus (MuLV) production in cells induced with halogenated pyrimidines has been investigated in several low leukemic strains of mice. Very few BALB/c or C57BL/6 (B6) induced embryo cells produce MuLV; this low frequency increases 10 to 50 fold in cells of the BALB/c × B6 F1 hybrid. Data from back-crosses of the F1 hybrid to each parent and from BALB/c × B6 recombinant inbred strains indicate that the phenotype of enhanced MuLV production results from interaction of two unlinked loci, dominant (+/+) alleles of which are carried by either parent. Genetic tests with BALB/c × B6 recombinant inbred strains confirm this two-locus model. The loci are designated Inc-1 and Inb-1 to signify their phenotypic detection by induction and the BALB/c or B6 strain of origin, respectively. Examination of hybrids of BALB/c and of B6 with other strains indicates that strains related in pedigree to BALB/c carry Inc-1, whereas those related to B6 carry Inb-1. Identification of genetic loci that specifically interact to enhance MuLV production after exposure to halogenated pyrimidines indicates the existence of mechanisms that regulate the induction or intracellular expression of endogenous MuLV.     

Isoelectric focusing of the inbred mouse antibody to bacterial alpha-amylase

In the IgG antibody response to bacterial alpha-amylase (B alpha A) assayed by the enzymatic procedure, C3H/He (C3) mice were high and C57BL/6 (B6) mice were low responders. High responsiveness was inherited as a dominant characteristic in (B6XC3)F1 hybrid mice. In these strains, the primary antibody response was analyzed for heterogeneity by isoelectric focusing (IEF). The IEF spectra were visualized with the use of the capacity of antibody to inhibit the amylase activity of antigen. Increases in the antigen dose and in the time interval between immunization and bleeding resulted in increases in antibody titers accompanied by strong staining of focused antibodies and by the expansion of the pH range where antibodies were focused. High responsiveness in C3 and F1 hybrid mice was also associated with the increase in intensity of stain and the rapid expansion of pH range of focused antibodies. Another strain difference was noted in the isoelectric point (pI) values of antibodies taken early in the primary response. B6 antisera contained those fractions of antibodies focusing over a more alkaline area than C3 antibodies. A similar strain difference in the pI values of antibodies occurred in the response to an irrelevant antigen, Taka-amylase A (TAA), suggesting that the hypervariable regions of antibody molecules play no major part in the strain difference observed. Antisera from F1 hybrid mice displayed bands covering the combined pH ranges of B6 and C3 spectrotypes.     

The effect of finoptin on doxorubicin accumulation in leukemia P-388 cells with induced resistance to the combination of finoptin and doxorubicin

Using hybrid mice BDF1 doxorubicin (Dx) accumulation has been determined in leukemia P388 cells (P388/0), P388 cells with induced resistance to Dx (P388/Dx) and P388 cells with induced resistance to the finoptin (Fp) + Dx combination (P388/Fp + Dx). It has been shown that Fp doesn't affect Dx accumulation in or elimination from leukemia cells P388/0 or P388/Fp + Dx. The resistance of P388/Fp + Dx cells to the Fp + Dx combination develops during 6 passages. It can be concluded that Fp application doesn't abolish the problem of tumor cells' resistance to cytostatics.     

Immature NK cells suppress dendritic cell functions during the development of leukemia in a mouse model

To analyze the mechanisms by which cancer cells escape from hosts' immune surveillance, we investigated the changes in immune status during the progression of leukemia induced by injecting mice with WEHI-3B cells. In the bone marrow (BM) of leukemic mice, only DX5(+)CD3(-) cells were continuously increased, despite the progression of leukemia. In addition, DX5(+)CD3(-) cells were rapidly increased in peripheral blood (PB) 20 days after inoculation. We also found that myeloid dendritic cells (DCs) expressing low levels of I-A(d) and having low allo-T cell stimulatory activity were markedly increased in PB and spleen. The increase in DX5(+) cells in BM was thought to be induced by soluble factors from leukemic cells. DX5(+) cells from leukemic mice were CD3(-), B220(-), Gr-1(-), CD14(-), CD94(-), Ly-49C/F(-), asialo GM1(+), CD25(+), CD122(+), Thy-1(bright), and c-kit(dim) and showed low killing activity against YAC-1 cells, suggesting that those DX5(+) cells were immature NK cells. NK cells from leukemic PB down-regulated the expression of I-A(d) on DCs, an effect mediated by TGF-beta. Moreover, these NK cells significantly suppressed the allo-T cell stimulatory activity of DCs, an effect requiring cell-to-cell contact between NK cells and DCs and thought to involve CD25. Importantly, NK cells from leukemic PB inhibited generation of autotumor-specific CTL induced by DCs in primary MLR or by DC immunization. In conclusion, we identified circulating immature NK cells with immunosuppressive activities. These cells may be important for understanding the involvement of the host immune system during the development of leukemia.     

Fresh and frozen-thawed sperm quality, nuclear DNA integrity, invitro fertility, embryo development, and live-born offspring of N-ethyl-N-nitrosourea (ENU) mice

Efficient collection, freezing, reliable archiving of sperm, and re-derivation of mutant mice are essential components for large-scale mutagenesis programs in the mouse. Induced mutations (i.e. transgenes, targeted mutations, chemically induced mutations) in mice may cause inherited or temporary sterility, increase abnormal sperm values, or decrease fertility. One purpose of this study was to compare the effect(s) on fresh and frozen-thawed sperm quality, spermatozoa DNA integrity, unassisted in vitro fertility (IVF) rate, in vitro embryo development rate to blastocysts, and live-born offspring rates in non-ENU (control) animals and the F1-generation of N-ethyl-N-nitrosourea (ENU)-treated male mice (765 mg/kg C57BL6/J or 600 mg/kg 129S1/SvImJ total dose). The second purpose was to determine the effect(s) of parental oocyte donor strain on in vitro fertilization, in vitro embryo development to blastocysts, and live-born offspring rates using sperm and unassisted IVF to re-derive animals from non-ENU control and ENU mice. Sperm assessment parameters included progressive motility, concentration, plasma membrane integrity, membrane function integrity, acrosome integrity, and DNA integrity. There were no significant differences in fresh sperm assessment parameters, DNA integrity, unassisted in vitro fertility rate, in vitro embryo development rate to blastocysts, and live-born offspring rates between non-ENU and C3B6F1/J or B6129S1F1/J ENU mice. In addition, there were no significant differences in frozen-thawed sperm assessment parameters and DNA integrity rates for non-ENU control and ENU C3B6F1/J or B6129SF1/J mice. In vitro fertilization and in vitro embryo development to blastocysts were effected from strain genetic variability (P < 0.05). However, the cryopreservation process caused an increase of DNA fragmentation in non-ENU control and ENU C3B6F1/J or B6129S1F1/J hybrid mice compared to fresh control sperm (P < 0.01). Unlike the combinations of hybrid sperm and hybrid oocyte, increasing frozen-thawed sperm DNA fragmentation decreased the embryo development rate to blastocyst compared to fresh sperm when C57BL6, C3H, or 129S inbred mice were used as oocyte donors (P < 0.05).     

Potentiation of Friend viral leukemogenesis by 9,10-dimethyl-1,2-benzanthracene in two strains of mice

The polycyclic aromatic hydrocarbon, 9,10-dimethyl-1,2-benzanthracene (DMBA) produced malignancy involving the spleen in SJL/J and B10SJF1 mice when injected ip at 500 micrograms per mouse either alone or in combination with threshold doses of Friend leukemia virus (FLV). The mice that received both chemical and virus died significantly sooner than mice that received either chemical or virus alone, and a synergism between DMBA and FLV was demonstrated in both the virus-resistant B10SJF1 hybrids and virus-sensitive SJL/J mice.     

Cytogenetic effect of mitomycin C and cytosine arabinoside on mice of different genotypes]

Cytogenetic effect of mitomycin C (MC) and cytosine arabinoside (CA) on bone marrow cells of male mice of the strains 101/HY, C57BL/6Y C,3H/SnY and of the (C3HX101) F1 hybrids was studied. The frequencies of cells with chromosome aberrations after the treatment with MC at a 5 mg/kg dose were 54,4%; 41,8%; 40,4% and 26,8% in 101H, B6, C3H/Sn mice and in the F1 hybrids (C3HX101) respectively. The frequencies of cells with chromosome aberrations after the treatment with CA at a 500 mg/kg dose were 25,2%; 17,8%; 10,8% and the 101/H, B6, C3H/Sn mice and in the F1 hybrids (C3HX101) respectively. Both mutagens induced the greatest number of chromosome aberrations in the 101/H strain and the smallest number in the F1 hybrid (C3HX101). A positive correlation was established between the levels of induced and spontaneous chromosome lesions.