Significance of transplacental hemorrhage in the induction of specific maternal unresponsiveness

Transplacental hemorrhage is reportedly detectable by erythrocytes containing fetal hemoglobin-F in the maternal circulation. The procedure in the present study is based on the premise that fetal hemoglobin is not eluted from red cells in blood smears by an acid buffer, whereas adult hemoglobin is removed. Erythrocytes containing hemoglobin-F were observed in blood smears of both virgin and pregnant BALB/c mice, but the relative number of these cells in the maternal blood increased during pregnancy, reached a peak around the time of parturition, and decreased thereafter. In BALB/c females pregnant by DBA/2 males, the relatively large numbers of acid-resistant erythrocytes in maternal blood were related to the maternal unresponsiveness to DBA/2 allografts. The fetal derivation of at least a fraction of these cells was suggested by the apparent activity of fetal immunogens in the maternal circulation. The blood of peripartum BALB/c mice multiparous by DBA/2 males was injected into normal, nonimmune BALB/c mice. The blood recipients were later challenged with an allotransplantable DBA/2 tumor. A low degree of immunity was indicated by a decreased size of tumor implants. Attempts to demonstrate vertical transmission of immune suppression from mothers to progeny were negative. These findings indicate that transplacental hemorrhage is a potential source of antigens involved in the induction of specific maternal unresponsiveness.     

Reaction of 7,12-dimethylbenz(a)anthracene with DNA of fetal and maternal rat tissues in vivo.

Pregnant BD-IX rats (21st day of gestation) received a single IV injection (15 mg/kg) of tritiated 7,12-dimethylbenz(a)anthracene (DMBA), A DOSE KNOWN TO INduce a high incidence of nervous-system tumors in the offspring. The animals were killed 12 h later and hydrocarbon-deoxyribonucleoside products from DNA of maternal and fetal tissues were separated on Sephadex LH-20 columns eluted with a 20-100% methanol gradient. Concentrations of the major DMBA-DNA adduct varied considerably, with highest values in maternal intestine, liverand lung, followed by spleen, kidney and brain. In fetal intestine and liver, concentrations were 34% and 16% lower than in the respective maternal organs whereas the reaction with cerebral DNA was 2 1/2 times higher in fetuses than in the pregnant mother. This indicates that there is no significant placental barrier to DMBA or DMBA metabolites involved in DNA binding and that rat fetuses participate in the metabolic formation of the ultimate carcinogen.     

Maternal effects of the scid mutation on radiation-induced transgenerational instability in mice

The results of a number of recent studies show that mutation rates in the offspring of irradiated parents are substantially elevated, however, the effect of parental genotype on transgenerational instability remains poorly understood. Here, we have analysed the mutation frequency at an expanded simple tandem repeat (ESTR) locus in the germline and bone marrow of the first-generation male offspring of control and irradiated male mice. The frequency of ESTR mutation was studied in the offspring of two reciprocal matings male symbol scid x female symbol BALB/c and male symbol BALB/c x female symbol scid, which were compared with that in BALB/c mice. In the offspring of the BALB/c x BALB/c and male symbol scid x female symbol BALB/c matings, which were conceived after paternal sperm irradiation, the frequency of ESTR mutation was significantly elevated in both tissues. In contrast, ESTR mutation frequency was only slightly elevated in the offspring of male symbol BALB/c x female symbol scid mating conceived after paternal irradiation. The results of this study suggest that the oocytes of scid females are unable to fully support the repair of double-strand breaks induced in paternal sperm which may in turn result in the elimination of cells/embryos containing high levels of DNA damage, thus partially preventing the manifestation of genomic instability.     

Whole body hyperthermia: a potent radioprotector in vivo

Interleukin-1 has been reported to be an effective radioprotective agent in mice subjected to lethal doses of irradiation. Production of Interleukin-1 can be increased by whole body hyperthermia. Therefore, whole body hyperthermia was assessed for its efficacy in protecting the lethal effects of ionizing radiation in DBA/2 mice. One hour of 40 degrees C +/- 0.2 whole body hyperthermia given 20 hr before 900 cGy total body irradiation protected 100% of DBA/2 mice from an LD 100/16 radiation dose (dose of irradiation that killed 100% of the mice in 16 days). Lethal doses of total body irradiation produced profound monocytopenia, decreased cellularity of thymus, spleen, and bone marrow, and suppressed Interleukin-1 production. Interleukin-1 production was determined using the thymocyte proliferation assay. Whole body hyperthermia accelerated recovery of blood leukocytes by up to 5 days post-total body irradiation in DBA/2 mice. Thymocytes, spleen, and bone marrow cells were activated by whole body hyperthermia, as assessed by the cell's response to Concanavalin A. This was accompanied by accelerated Interleukin-1 generation. Our results provide the first evidence that whole body hyperthermia acts as a potent radioprotector in vivo, effects that may be mediated by Interleukin-1.     

Oncogenicity of friend-virus-infected cells: Determination of origin of spleen colonies by the H-2 antigens as genetic markers

Spleen cells from mice infected with Friend leukemia virus (FLV) inoculated by the intravenous route give rise to macroscopically visible colonies in the spleens of normal F₁ histocompatible hybrid hosts. A study of H-2 antigens as generic markers for identification of strains of origin of cells constituting the spleen colonies was undertaken. The standard cytotoxic test was demonstrated to be suitable for characterizing the H-2 antigens present on the surface of spleen cells from normal or FLV-leukemic parents or F₁ hybrid mice. Individual colonies dissected out of the spleen of (C3H × C57BL/6) F₁ recipients (H-2^k/H-2^b), 10 days after the intravenous graft of FLV-infected spleen cells of C3H origin (H-2^k), were all sensitive to anti-C57BL/6 antibodies. In the same way, colonies obtained from the spleens of (DBA/2 × C57BL/10) F₁ recipients (H-2^d/H-2^b) grafted with DBA/2 leukemic spleen cells (H-2^d) were all sensitive to both anti-H-2^b and anti-H-2^d antibodies. These results directly prove that the main cell population constituing a spleen colony arises from the recipient. The authors conclude that the spleen colonies do not result from the neoplastic proliferation of injected donor cells but rather from the multiplication of host cells transformed by Friend virus produced by the grafted cells.     

IFN-α1 gene transfection completely abolishes the tumorigenicity of murine B16 melanoma cells in allogeneic DBA/2 mice and decreases their tumorigenicity in syngeneic C57BL/6 mice

The murine B16 melanoma (H-2^b) was transfected with a retroviral vector containing the mouse IFN-α₁ gene. IFN-α₁-transfected cells produced IFN-α in vitro and exhibited an altered phenotype characterized by a decreased rate of multiplication, enhanced expression of H-2 antigens, an antiviral state to VSV, and decreased pigmentation. Control and IFN-α₁-transfected cells were tested for their ability to grow in syngeneic (H-2^b) CS7B1/6 and allogeneic (H-2^d) DBA/2 mice. IFN-α₁producing B16 clones were less tumorigenic after s.c, i.p., and i.v. routes of injection than IFN-non-producer BI6 clones in syngeneic CS7B1/6 mice. IFN-α₁-producing B16 cells were, however, totally rejected by allogeneic DBA/2 mice regardless of the routes and inocula tested, while control B16 cells grew in and killed DBA/2 mice. The total rejection of IFN-α₁-transfected B16 cells in allogeneic mice appeared to be dependent on T cells as these cells grew in DBA/2 nude mice. Incubation of IFN-α-producing clones with anti-mouse IFN-α/β prior to injection into C57BI/6 mice did not enhance their tumorigenicity. Likewise, injection of C57BI/6 and DBA/2 mice with antibody to IFN-α/β did not enhance the tumorigenicity of IFN-α₁-transfected cells. C57B1/6 mice immunized with irradiated IFN-α₁ cells were only slightly protected against a subsequent challenge with parental B16 cells. In contrast, DBA/2 mice immunized with irradiated IFN-α₁ cells exhibited tumor-specific, long-lasting immunity to subsequent challenge with parental B16 cells. © 1995 Wiley-Liss, Inc.     

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.     

Modification of transplacental tumorigenesis by 3-methylcholanthrene in mice by genotype at the Ah locus and pretreatment with beta-naphthoflavone

Transplacental lung and liver tumorigenesis in the mouse by 3-methylcholanthrene (MC) was assessed as a function of inducibility of MC metabolism in fetus and in mother, and of pretreatment of the mothers with a noncarcinogenic inducer, beta-naphthoflavone (beta NF). Pregnant (C57BL/6 X DBA/2)F1 females (genotype Ahb Ahd, inducer responsive) mated to DBA/2 males received 45 or 100 mg/kg MC on gestation day 17, and DBA/2 females (genotype Ahd Ahd, nonresponsive) mated to F1 males were given 5 or 30 mg MC/kg. These crosses generated both responsive and nonresponsive offspring. Phenotype and tumor incidences were determined at 13 months of age. The transplacental action of MC was dose dependent and resulted in more lung and liver tumors in induction-responsive offspring than in nonresponsive littermates in most comparisons. beta NF alone did not result in increased numbers of tumors. Significant, complex effects were seen when the mothers were pretreated with beta NF (150 mg/kg) on gestation day 15, before MC on day 17. The beta NF pretreatment protected the fetuses of the F1 mothers: there was a significant overall 30 to 50% reduction in numbers of lung and liver tumors. The greatest effect was seen in the induction-responsive males, who experienced a 50% reduction in both incidence and multiplicity of lung tumors after 100 mg MC/kg, compared with males exposed to MC only. By contrast, beta NF pretreatment of DBA mothers had no general effect but rather potentiated the action of the 5 mg MC/kg dose on multiplicity of lung tumors in inducible males, causing a significant 4-fold increase. It also caused a 60% increase in inducible male liver tumor multiplicity when given before the 30 mg MC/kg dose. Thus, beta NF pretreatment was protective when the mother was inducible, especially in the inducible fetuses of such a mother, but when the mother was noninducible the beta NF pretreatment had no effect in some situations and potentiated the action of the carcinogen in others, mainly in inducible fetuses. These results underscore the fact that induced maternal and fetal metabolism contribute to risk of transplacental tumorigenesis by MC in qualitatively opposite ways.     

Tumour induction by methyl-nitroso-urea following preconceptional paternal contamination with plutonium-239.

We have investigated the possibility that transgenerational effects from preconceptional paternal irradiation (PPI) may render offspring more vulnerable to secondary exposure to an unrelated carcinogen. 239Pu (0, 128 or 256 Bq g(-1)) was administered by intravenous injection to male mice, 12 weeks before mating with normal females. Two strains of mouse were used -- CBA/H and BDF1. Haemopoietic spleen colony-forming units (CFU-S) and fibroblastoid colony-forming units (CFU-F), a component of their regulatory microenvironment, were assayed independently in individual offspring at 6, 12 and 19 weeks of age. Bone marrow and spleen from each of these mice were grown in suspension culture for 2 or 7 days for assessment of chromosomal aberrations. Female BDF1 were injected with methyl-nitroso-urea (MNU) as a secondary carcinogen at 10 weeks of age and monitored for onset of leukaemia/lymphoma. Mean values of CFU-S and CFU-F were unaffected by preconceptional paternal plutonium-239 (PP-239Pu), although for CFU-F in particular there was an apparent increase in variation between individual animals. There was significant evidence of an increase in chromosomal aberrations with dose in bone marrow but not in spleen. By 250 days, 68% of MNU-treated control animals (no PPI) had developed thymic lymphoma (62%) or leukaemia (38%). The first case arose 89 days after MNU administration. In the groups with PPI, leukaemia/lymphoma developed from 28 days earlier, rising to 90% by 250 days. Leukaemia (65%) now predominated over lymphoma (35%). This second generation excess of leukaemia appears to be the result of PPI and may be related to inherited changes that affect the development of haemopoietic stem cells.     

The effect of pregnancy on the growth of primary methylcholanthrene sarcoma isografts

Primary isografts of a highly immunogenic methylcholanthrene tumor were injected into pregnant C57/BL mice. Tumor growth was studied and compared to isografts injected into virgin C57/BL mice preimmunized with fetal antigens. Significant in vivo enhancement of MCA tumor growth was noted in both intra- and interstrain pregnant mice compared with virgin controls. In addition, active preimmunization of virgin mice with hybrid fetal liver did not result in rejection of primary tumor isografts, suggesting that fetal antigens did not contribute to the immunogenicity of this MCA tumor.     

Sensitized T lymphocytes render DBA/2 beige mice responsive to IFN α/β therapy of friend erythroleukemia visceral metastases

Interferon α/β (IFN α/β) is highly effective in inhibiting the development of Friend erythroleukemia cell (FLC) visceral metastases in DBA/2 mice injected intravenously (i.v.) with FLC, but does not protect FLC-injected DBA/2 beige (bg/bg) mice. Use of IFN α/β-resistant FLC indicated that IFN was acting through host mechanisms in DBA/2 mice and thus pointed to a defect in some host mechanism in bg/bg mice essential for IFN's anti-metastatic action. We undertook experiments to restore in bg/bg mice the marked anti-FLC meta-static effect of IFN a/p observed in DBA/2 and +/bg mice. Adoptive transfer of spleen cells from normal syngeneic mice to IFN-treated bg/bg mice was ineffective, but the transfer of splenic T lymphocytes from FLC-immunized DBA/2 or +/bg mice markedly increased the survival time of FLC-injected bg/bg mice provided that these mice were also treated with IFN a/p. Neither treatment alone resulted in an increase in survival time. As few as 1 × 10⁷ immune spleen cells were effective in IFN-treated FLC-injected bg/bg mice. The T-cell immune response to FLC of bg/bg mice was diminished compared with that of +/bg mice. Likewise, only combination therapy of immune spleen cells and IFN α/β resulted in an increased survival time of ESb-lymphoma-injected bg/bg mice. Our results indicate the essential participation both of T-cell-mediated immune mechanisms and of IFN α/βin the inhibition of FLC visceral metastases.     

Emerging therapeutic options for breast cancer chemotherapy during pregnancy.

BACKGROUND: Breast cancer is the commonest solid tumor observed during pregnancy. Anthracycline-based chemotherapy is feasible during the 2nd and 3rd trimesters of pregnancy, but few data are available on recent and highly active drugs taxanes, vinorelbine and anti-HER-2 agents in this setting. PATIENTS AND METHODS: We carried out a comprehensive review of reports documenting the use of taxanes, vinorelbine, trastuzumab and lapatinib during pregnancy in the English literature, in order to evaluate their safety profile in pregnant patients. RESULTS: Twenty-four pregnancies are described, in which no grade 3-4 maternal toxicity nor malformation in the offspring was reported. Whereas only one report studied the pharmacokinetics of paclitaxel (Taxol) during pregnancy, several preclinical reports indicate that the placental P-glycoprotein could prevent the transplacental transfer of taxanes and vinorelbine. The use of trastuzumab was associated with the occurrence of anhydramnios in three of six cases. CONCLUSION: The administration of recent drugs taxanes and vinorelbine seems feasible during the 2nd and 3rd trimesters of pregnancy, with a favorable toxicity profile. In contrast, anti-HER-2 agents may obscure the normal development of the fetal kidney, and should be avoided during pregnancy.     

Formation and persistence of benzo[a]pyrene--DNA adducts in different tissues of C57BL/10 and DBA/2 mice

Synchronous fluorescence spectrophotometry (SFS) developed to study benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE)--DNA adducts was used to measure the formation and disappearance of DNA adducts in the lung, liver, kidney, spleen and small intestine of genetically responsive C57BL/10 (B10) and nonresponsive DBA/2 (D2) mice. After single stomach intubation of 100 mg/kg of benzo[a]pyrene (B[a]P) in both strains, binding of BPDE to DNA reached a peak 48 h after treatment. However, the levels of binding in the lung, liver, kidney and spleen were higher in D2 than in B10 mice. In contrast to this, in the small intestine the higher level of BPDE binding was found in B10 mice and reached its maximum 24 h earlier. Thereafter a very rapid drop in the level of BPDE--DNA adducts to a value of approximately 50% after 48 h was observed in this tissue. In the other tissues of the B10 mice the rate of adducts removal was slower, but by 14 days after treatment 90-100% of adducts were removed. In the D2 mice up to the 4th day after treatment the rates of removal of the BPDE--DNA adducts were similar to that of the B10 mice. Thereafter the level of bound hydrocarbon decreased at a slower rate. During the whole period after B[a]P treatment distinct differences between organs in the amount of BPDE--DNA adducts were observed. In D2 mice the highest level of binding was found in the spleen followed by the lung, kidney, liver and small intestine. In B10 mice the highest level of binding was observed in the DNA of small intestine. The data suggest that the decreased rate of B[a]P metabolism in D2 mice may be at least in some tissues the reason of higher binding of BPDE--DNA adducts in comparison with B10 mice.     

Changes of serum thymic factor levels in Friend leukemia virus-infected mice.

Sera and spleen cells from DBA/2 and BALB/c mice were sampled at various time intervals after infection with Friend leukemia virus (FLV, polycythemic strain) and assayed for the presence of serum thymic factor (STF) and theta-positive cells, respectively.A pronounced and dose-dependent decrease of STF levels was observed in DBA/2 mice as early as 48 h after infection; STF levels were decreased in BALB/c mice, too, but the effect was less marked and long-lived than in DBA/2 mice.In close parallelism to the fall of STF levels in the sera, theta-positive cells were also found to be markedly decreased in the spleens of DBA/2 mice and, to a lesser extent, in BALB/c mice. Thetapositive cells were assayed by measuring the sensitivity to azathioprine of spleen rosette-forming cells.Both the fall of STF levels and the decrease of theta-positive spleen cells do not persist longer than 4 weeks and are not, therefore, related to the state of overt leukemia.Conceivably, though, these changes, that appear to be virus-related, may influence the early fate of FLV-transformed cells by lowering some thymus-dependent functions which may be relevant to the immunological surveillance.     

Carcinogenicity of dapsone in mice and rats

Dapsone (4,4′-diamino-diphenyl sulfone) has been tested for possible carcinogenicity in long-term animal experiments. BDIV rats and C₇BL mice received a 3.5% aqueous suspension of dapsone by intragastric intubation. Treatment was started in pregnant females during the last part of pregnancy, continued during lactation, then given to the offspring after weaning, five times a week for 104 weeks. The dose administered was 100 mg/kg to both rats and mice; total doses ranged from 10–16 g per rat and 1.2–1.4 g per mouse. Separate groups of animals received a combined treatment of dapsone with urethane or benzo (α) pyrene, to investigate the possible additive or synergistic action of dapsone with known carcinogens, as well as the possible inhibiting effect of dapsone on carcinogenesis. Unusual tumours, viz. spleen sarcomas (related to severe fibrosis of the spleen) were detected in male rats, and higher morbidity from C-cell thyroid carcinomas was observed in treated rats of both sexes than in control rats. There was no evidence that dapsone can modify the action of other chemical carcinogens. It was noted that: (1) although the increase in the incidence of turnours in dapsone-treated animals over that observed in untreated controls is statistically significant, the increase is relatively low; (2) the tumours appeared after lifetime treatment with maximum tolerated doses; (3) in rats, spleen sarcomas were observed mostly in males; this may indicate a possible hormone-dependence of the observed carcinogenic effect. The present results therefore provide only limited evidence of carcinogenicity of dapsone in rats.     

Effect of combination treatment with cyclophosphamide and isogeneic or allogeneic spleen and bone marrow cells in leukemic (l1210) mice

Generalized leukemia was observed on day 3 following intra-peritoneal inoculation of leukemic (L1210) ascites cells in CDF₁ mice. On day 3 after tumor implantation, residual viable leukemic cells were detected in the peritoneal cavities and spleens of leukemic mice 6 h following treatment with 180 mg/kg of cyclophosphamide. Mice receiving weekly intraperitoneal injections of X-irradiated leukemic (L1210) cells for 6 weeks were resistant to a challenge of tumor cells. When incubated in vitro, spleen and bone marrow cells of immune mice were able to inactivate viable leukemic cells, as evidenced by failure of tumor growth in mice inoculated with these cells. Leukemic mice injected with immune spleen or bone-marrow cells from isogeneic mice following treatment with cyclophosphamide survived a 60-day observation period. In one such experiment 90-day survivors were able to resist re-inoculation of tumor cells. Leukemic (DBA/2) mice inoculated with allogeneic spleen cells following cyclophosphamide treatment survived for longer periods than mice injected with isogeneic spleen cells.     

Genetic separation of GvL and GvH reactivity in new recombinant-inbred tumor-resistant mouse strains

From a cross between a tumor-susceptible syngeneic mouse strain (DBA/2) and a tumor resistant MHC congenic strain (B10.D2) new recombinant inbred mouse strains were established over many generations of inbreeding and tumor resistance selection. The resistance selected against one DBA/2 derived malignant tumor (ESb) extended to other DBA/2 malignant tumors (SL 2, MDAY-D2) and was thus of more general significance. Since tumor resistance had an immunological basis and since the two parental strains differed in multiple minor histocompatibility antigens (H) as well as in viral superantigens (vSAGs) we determined specificities of cytotoxic T lymphocyte (CTL) responses in vitro. All CTL responses from tumor resistant strains showed not only antitumor reactivity but also rather strong anti-minor H reactivity. There was no relationship between cytolysis and the DBA/2 type vSAG-7 (Mls(a)) expression. We also tested the capacity of immune cells from 7 resistant lines to transfer graft versus leukemia and graft versus host reactivity to ESb tumor bearing DBA/2 mice. Immune cells from one subline were capable of transfering complete protection without development of chronic GVH over a period of 4 months. The resistant parental line B10.D2 and most of the other sublines also were able to transfer GvL reactivity but this was usually associated later with chronic GVH disease caused mortality. These results demonstrate the potential of this genetic approach to separate GvL from GvH reactivity.     

Loss of marrow allograft resistance in mice with transplanted methylcholanthrene-induced sarcomas.

To determine if the effector cells responsible for allogeneic marrow stem cell rejections were suppressed in mice with tumors, C57BL/6 (B6) mice were inoculated with 3-methylcholanthrene (MCA)-induced sarcoma cells. When the tumor reached 2.0--2.5 cm in diameter, these mice and control B6 and (BALB/c times A)F1 (CAF1) uninoculated animals were irradiated and given BALB/c marrow cells in the first of a two-step "stem cell rescue" experiment. Four days later, spleen cells of the primary hosts were reinoculated into irradiated CAF1 secondary hosts compatible with BALB/c marrow cells and immunized against B6 antigens. Splenic uptake (percent) of 125I-5-iodo-2'-deoxyuridine 5 days after spleen cell regrafting was used as a measure of cell proliferation and reflected growth of the stem cells in the primary hosts. BALB/c stem cells grew as well in B6 mice with tumors as in CAF1 primary hosts but were rejected by B6 controls. Seeding efficiency of BALB/c stem cells 6 hours after infusion of marrow cells and growth of syngeneic B6 stem cells were enhanced twofold in spleens of tumor-bearing B6 mice. To exclude the possibility that enhanced seeding resulted in greater survival of allogeneic stem cells, more DBA/2 marrow cells were infused into control B6 primary hosts than into tumor-bearing B6 and control DBA/2 mice. Control B6 mice resisted growth of even 7.5 times 10(6) DBA/2 marrow cells, whereas B6 tumor bearers allowed growth of 2.5 times 10(6) cells. No "suppressor cells" capable of inhibiting marrow cell allograft reactions were detected in spleens of tumor-bearing mice. Thus transplanted syngeneic MCA-induced sarcomas abrogated the ability of mice to reject allogeneic marrow stem cells.