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M L Kripke

Publications and source records attributed to M L Kripke.

216 records · Page 12Linked to original sources

Time of appearance and histology of tumors induced in the dorsal skin of C3Hf mice by ultraviolet radiation from a mercury arc lamp.

The time course of skin tumor induction was determined in hair-clipped inbred agouti C3Hf mice irradiated three times per week with a medium-pressure quartz-mercury lamp; 4 different UV doses were used. Although the ears were also exposed to the radiation, in the 3 groups given the highest doses no ear tumors were observed by the time each animal had developed at least 1 tumor on its back. No tumors were found in the animals receiving the lowest UV dose. In the group receiving the highest dose, males developed tumors earlier than did females; this trend continued in the lower dose groups. Many tumors that developed in the back skin were well-differentiated squamous cell carcinomas. Others were less well-differentiated squamous cell carcinomas. Others were less well defined so that the cell of origin was difficult to determine. In the group receiving the highest UV dose, the squamous cell carcinomas were few, whereas at the lower doses they predominated.

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Effects of trypan blue treatment on the immune responses of mice.

It has been reported that trypan blue treatment decreases the nonspecific resistance of mice to transplanted tumors and inhibits the in vitro cytotoxic activity of activated macrophages. We wished to determine whether this effect of trypan blue could be due to a selective inhibition of certain macrophage functions or whether it reflected a broader form of immunosuppression. We therefore tested the effects of trypan blue on a variety of immunological responses. Treatment of mice with trypan blue delayed their rejection of skin allografts and transplants of a highly antigenic syngeneic ultraviolet light-induced tumor. Trypan blue treatment of either donor or recipient decreased the local graft-versus-host reaction. Filtration of lymph node cells from trypan blue-treated donors on a nylon wool column before use in the graft-versus-host assay abrogated the depressive effect of trypan blue. A transient reduction in the blastogenic response of spleen cells to concanavalin A and lipopolysaccharide mitogens was observed after a single injection of trypan blue, but the response of lymph node cells was unaffected. The depressed response of splenic lymphocytes was not entirely reversed by removal of adherent cells. The primary and secondary hemagglutinin responses to sheep erythrocytes were unaffected in trypan blue-treated mice, and the proportion and phagocytic activity of thioglycolate-induced peritoneal macrophages were also unaltered. We conclude that treatment of mice with trypan blue selectively inhibits certain macrophage functions but, at high doses, it can also inhibit some lymphocyte activities.

Agglutinins↗

In vitro reactivity of splenic lymphocytes from normal and UV-irradiated mice against syngeneic UV-induced tumors.

Skin tumors induced in mice by chronic ultraviolet (UV) irradiation are highly antigenic and are frequently immunologically rejected upon transplantation to normal syngeneic recipients. In this study we characterized this immune response with an in vitro microcytotoxicity test. Cytotoxic activity was present in the spleen cells of mice given a single injection of syngeneic UV-induced fibrosarcoma cells. After removal of adherent spleen cells, the remaining splenic lymphocytes were specifically cytotoxic for the immunizing tumor and showed no cross-reactivity with other syngeneic UV-induced or methylcholanthrene-induced tumors of similar histologic type. The level of cell-mediated reactivity against UV-induced tumors was quite high compared to that obtained with syngeneic tumors induced by methylcholanthrene, and the cytotoxicity was attributable to a population of theta antigen-bearing lymphocytes. With this in vitro test, we compared the response of normal mice, which reject a syngeneic tumor challenge, with that of UV-irradiated mice, in which the syngeneic UV-induced tumors grow progressively. After tumor cell inoculation, lymphocytes form the unirradiated (regressor) mice showed a high degree of cytotoxicity that reached a maximum level 8 days after injection. In contrast, no reactivity could be detected in the spleens of tumor-challenged UV-irradiated (progressor) mice.

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Immunologic parameters of ultraviolet carcinogenesis.

Skin tumors induced in mice by UV light are usually immunologically rejected by normal syngeneic recipents. We evaluated the immune status of primary hosts against these highly antigenic tumors immediately after surgical removal of the primary tumor. All primary hosts were susceptible to challenge with their autochthonous tumors, though most of these were rejected by untreated control mice. Primary hosts were also susceptible to challenge with isografts of antigenically dissimilar UV-induced neoplasms. The susceptibility of the primary hosts to tumor challenge was probably induced by chronic exposure to UV light, since UV-irradiated non-tumor-bearing mice were also susceptible to challenge with these tumors. Although UV-treated mice were unalbe to reject these syngeneic tumors, they could reject skin and tumor allografts. Further, UV irradiation did not interfere with the second-set rejection of syngeneic UV-induced tumors in mice that were specifically immunized before UV treatment.

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Carcinogenicity of combined ultraviolet B radiation and psoralen plus ultraviolet A irradiation treatment of mice.

Psoralen plus ultraviolet A (PUVA) therapy and UVB phototherapy are frequently used in the treatment of psoriasis and other skin diseases. Both treatments are thought to be carcinogenic, but little is known about their interaction in the induction of skin cancer. Tumors induced in mice treated with both PUVA and UVB, either given sequentially or concurrently, seemed to be more antigenic as a group than tumors treated by PUVA alone, as determined by their lower frequency of growth when transplanted into naive mice. In this study, we treated C3H mice with a subcarcinogenic dose of UVB radiation for 4 weeks, followed by PUVA treatment for 41 weeks (sequential experiment) or with both UVB radiation (minimal carcinogenic dose) and PUVA for 41 weeks (concurrent experiment) and monitored the development of skin cancers. Although a few tumors appeared earlier in the groups treated with both UVB and PUVA in both experiments, no significant differences were observed in the rate of tumor development in mice treated with UVB and PUVA versus those treated with PUVA alone.

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