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M L Kripke

Publications and source records attributed to M L Kripke.

At least 199 records · Page 11Linked to original sources
PubMed1979

Further characterization of immunological unresponsiveness induced in mice by ultraviolet radiation. Growth and induction of nonultraviolet-induced tumors in ultraviolet-irradiated mice.

Ultraviolet (UV)-irradiated mice were compared with unirradiated mice for their susceptibility to primary and transplanted tumors etiologically unrelated to UV radiation. Although UV-irradiated mice are unable to reject transplants of highly antigenic syngeneic tumors induced by UV light, the growth of syngeneic, non-UV-induced tumors generally was not accelerated in these animals. Furthermore, UV-irradiated mice were no more susceptible to the induction of primary leukemias, mammary tumors, or sarcomas than were unirradiated animals. Tests of immune responses to weak transplantation antigens showed that UV-irradiated mice rejected H-Y-incompatible skin grafts as vigorously as did normal animals, and that the primary in vitro cytotoxic responses of spleen cells from UV-irradiated mice to trinitrophenyl (TNP)-modified syngeneic cells and to Hh antigens were unaffected. We conclude that the susceptibility of UV-irradiated mice to challenge with UV-induced tumors represents a selective unresponsiveness, and that it is not attributable to a generalized deficiency in the immune response to tumor-specific antigens or to weak transplantation antigens.

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PubMed1979

Influence of immune status on the metastasis of three murine fibrosarcomas of different immunogenicities.

Three fibrosarcomas of different immunogenicities were tested for their ability to form spontaneous and experimentally induced metastases in normal, sham-suppressed, immunosuppressed, and immunologically restored syngeneic mice. Immunosuppression, achieved by adult thymectomy and sublethal X-irradiation (450 R), affected experimental metastasis of the three tumors in different ways. Upon i.v. injection, the highly immunogenic fibrosarcoma formed more pulmonary tumor colonies in immunosuppressed mice than in normal, sham-suppressed (sham thymectomy and 450 R), or immunologically reconstituted animals (thymectomy, X-irradiation, plus 10(7) normal syngeneic lymphocytes given i.v.). A fibrosarcoma of intermediate immunogenicity also formed more pulmonary metastases in immunosuppressed recipients, but this increase could not be reversed by reconstitution with 10(7) lymphocytes. In contrast, the least immunogenic tumor formed fewer pulmonary tumor colonies in immunosuppressed mice than in normal, sham-suppressed, or immunologically reconstituted mice. We conclude that the role of the immune system in experimental cancer metastasis varies for different tumors and that tumor immunogenicity is an important factor in the relationship between host immunity and tumor dissemination.

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PubMed1978

Accelerated growth of syngeneic tumors in mice treated with methylcholanthrene.

BALB/c and C3H- mice were given a single injection of methylcholanthrene (MCA) and were tested at various times thereafter for immunologic reactivity and resistance to syngeneic tumor challenge. MCA treatment did not affect the rejection of H-2-incompatible tumor allografts, the rejection of H-2-compatible skin allografts, or the induction of delayed hypersensitivity to DNCB as measured by footpad challenge. In contrast, mice treated with MCA exhibited an increase susceptibility to challenge with several syngeneic ultraviolet-induced and MCA-induced fibrosarcomas. These studies demonstrate that in the autochthonous host the measurement of host immune status by in vivo cell-mediated immune responses to exogenous antigens does not necessarily predict the host response to tumor growth.

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PubMed1978

Further studies on the tumor-specific suppressor cells induced by ultraviolet radiation.

Recent studies have suggested that the immunologic unresponsiveness of UV-irradiated mice against UV-induced fibrosarcomas might be due to the presence of suppressor lymphoid cells. In these experiments, we present additional evidence that suppressor lymphoid cells are present in lymph nodes and spleens of UV-irradiated mice and demonstrate that these cells are enriched after incubation on nylon wool columns, that they are inactive after treatment with anti-theta serum and complement, and that they are effective for at least 7 weeks after transfer to lethally x-irradiated mice. Splenectomy of UV-treated mice before tumor challenge did not restore their anti-tumor reactivity. The UV-induced suppressor cells appear to be specific for syngeneic UV-induced tumors, since they did not suppress the rejection of an allogeneic UV-induced tumor or two chemically induced syngeneic tumors.

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PubMed1978

Ultraviolet carcinogenesis in T-cell-depleted mice.

The induction of skin tumors by chronic UV irradiation was compared in normal C3H/HeN(MTV-) mice, T-cell-depleted mice, and T-cell-depleted mice reconstituted with thymus grafts. The T-cell-depleted mice were thymectomized as young adults, lethally X-irradiated, and repopulated with neonatal liver cells. Skin tumors appeared earlier in the immunosuppressed T-cell-depleted mice than in the normal mice. However, tumors developed most rapidly in the group that was T-cell depleted and immunologically restored with thymus grafts. In the latter group, most of the tumors were squamous cell carcinomas, whereas in the normal mice, fibrosarcomas predominated. These experiments illustrated the limitations of this approach to studying the role of the immune response in carcinogenesis.

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PubMed1978

Immunologic aspects of tumor induction by ultraviolet radiation.

Chronic treatment of mice with UVR not only induced skin cancer but also produced a systemic change that interfered with host resistance against these tumors. The studies leading to the this conclusion were prompted by the discovery that most tumors induced in C3H mice by chronic UV irradiation were immunologically rejected following transplatation to normal syngeneic recipients. This raised the question of why these tumors were able to grow progressively in the autochthonous host without being destroyed immunologically. We found that after a short course of UV treatment, the UV-irradiated mice lost their ability to reject transplanted UV-irradiated mice lost their ability to reject transplanted UV-induced tumors, even though such transplants were rejected by unirradiated animals. The growth of the transplanted tumors in UV-treated mice resulted from a systemic alteration in the animals that was induced by UV irradiation of the skin.

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PubMed1977

Metastasis results from preexisting variant cells within a malignant tumor.

Clones derived in vitro from a parent culture of murine malignant melanoma cells varied greatly in their ability to produce metastatic colonies in the lungs upon intravenous inoculation into syngeneic mice. This suggests that the parent tumor is heterogeneous and that highly metastatic tumor cell variants preexist in the parental population.

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PubMed1977

Systemic alteration induced in mice by ultraviolet light irradiation and its relationship to ultraviolet carcinogenesis.

Chronic irradiation of mice with ultraviolet (UV) light produces a systemic alteration of an immunologic nature. This alteration is detectable in mice long before primary skin cancers induced by UV light begin to appear. The alteration results in the failure of UV-irradiated mice to reject highly antigenic, transplanted UV-induced tumors that are rejected by unirradiated syngeneic recipients. The immunologic aspect of this systemic alteration was demonstrated by transferring lymphoid cells from UV-irradiated mice to lethally x-irradiated recipients. These recipeints were unable to resist a later challenge with a syngeneic UV-induced tumor, whereas those given lymphoid cells from normal donors were resistant to tumor growth. Parabiosis of normal mice with UV-irradiated mice, followed by tumor challenge of both parabionts with a UV-induced tumor, resulted in the growth of the challenge tumors in both UV-irradiated and unirradiated mice. Splenic lymphocytes from tumor-implanted UV-treated mice were not cytotoxic in vitro against UV-induced tumors, whereas under identical conditions cells from tumor-implanted, unirradiated mice were highly cytotoxic. Our findings suggest that repeated UV irradiation can circumvent an immunologic mechanism that might otherwise destroy nascent UV-induced primary tumors that are strongly antigenic.

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PubMed1977

In vivo immune responses of mice during carcinogenesis by ultraviolet irradiation.

In these experiments, we tested in various in vivo assays the immune responses of inbred C3H/HeN(MTV-) (C3H-) mice during carcinogenesis by chronic exposure to UV irradiation. Although the UV-treated mice were unable to reject syngeneic UV-induced tumor transplants, they rejected H-2-incompatible tumor allografts and H-2-compatible skin allografts. The primary hemagglutinin response to sheep red blood cells was normal in these mice, as were the induction of a local graft-versus-host reaction with lymphoid cells from UV-irradiated donors and the induction of an inflammatory response to dimethyl sulfoxide in the footpads of UV-treated mice. An early transient depression of two reactions in UV-irradiated mice occurred: delayed hypersensitivity to dinitrochlorobenzene measured by footpad swelling and the graft-versus-host reaction in UV-irradiated recipients measured by the use of the popliteal lymph node weight gain assay. Both of these reactions returned to a normal level before the development of primary tumors. We conclude that the inability of UV-irradiated mice to reject syngeneic and autochthonous UV-induced tumors was not due to a generalized immunosuppressive effect of chronic UV irradiation.

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PubMed1977

In vitro reactivity of macrophages and lymphocytes from ultraviolet-irradiated mice.

In these experiments we examined the ability of lymphocytes and macrophages from UV-treated mice of the inbred strain C3H/HeN(MTV-) to respond in vitro to nonspecific stimuli. Spleen and lymph node cells from UV-treated mice exhibited blastogenic responses to concanavalin A, phytohemagglutinin, and lipopolysaccharide that were equal to those of lymphoid cells from normal animals. Neither the induction of peritoneal exudate cells by inflammatory agents nor the phagocytic activity of peritoneal macrophages was affected by UV irradiation. Furthermore, no reduction occurred in the in vitro tumoricidal capacity of peritoneal macrophages from UV-treated mice after in vitro activation with xenogeneic lymphokines or endotoxin. We concluded that chronic UV irradiation does not lead to a generalized suppression of the immune system in mice.

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