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M L Kripke

Publications and source records attributed to M L Kripke.

At least 127 records · Page 7Linked to original sources
PubMed1989

The role of ultraviolet radiation in the induction of melanocytic skin tumors in inbred mice.

The purpose of these studies was to determine whether ultraviolet radiation contributes to the induction of cutaneous melanocytic tumors in mice. At 4 days of age, C3H/HeNCr(MTV-) mice received an initiating dose of 7,12-dimethylbenz(a)anthracene, followed by twice weekly applications of croton oil. Of the mice treated with this protocol, 31% developed melanoma. The addition of chronic doses of ultraviolet radiation (UVR) to the carcinogen treated site dramatically accelerated the development of the melanomas. Substituting UVR for the initiator or the promoter in this two-stage carcinogenesis model resulted in the development of a few melanocytic tumors (less than 10%). These experiments demonstrate that UVR accelerated the development of cutaneous melanocytic tumors induced in mice by chemical carcinogens and participated in the induction of these tumors by serving as a weak initiator or promoter.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1989

Variations in the number and morphology of Langerhans' cells in the epidermal component of squamous cell carcinomas.

We investigated the number and morphology of Langerhans' cells in the epidermal component of squamous cell carcinomas located on the sun-exposed skin of 10 patients. Using adenosine triphosphatase-stained epidermis from the tumors, we compared the Langerhans' cells in squamous cell carcinoma with those in nontumorous skin specimens from the same patient. The nontumorous skin specimen was obtained from either sun-exposed perilesional or non-sun-exposed sites. In three patients a normal number and almost normal morphology of Langerhans' cells were observed within the epidermal component of the tumor. One patient showed a normal number but a profound alteration of the morphology of the cells. In the remaining six patients, a significant decrease in the number of Langerhans' cells was observed. Langerhans' cells within the epidermal component of the tumors of these patients exhibited morphologic alterations in that they were mainly round or oval rather than highly dendritic. In none of our patients was the number of Langerhans' cells in the tumor increased. We conclude that a decreased number and altered morphology of Langerhans' cells occur in some, but not all, squamous cell carcinomas of the skin, and that there is no apparent difference between the number of Langerhans' cells in sun-exposed vs unexposed skin from the same individual.

Aged↗
PubMed1988

Differential extraction of tumor-specific antigens from two ultraviolet light-induced murine fibrosarcomas with the use of 1-butanol.

The purpose of this study was to investigate the immunobiological characteristics of the tumor-specific cell surface antigen expressed by the UV-induced murine fibrosarcoma, UV-2240. UV-2240 is classified as a regressor UV tumor because it is immunologically rejected by normal syngeneic mice but grows in immunocompromised or UV-irradiated hosts. The strong tumor-specific rejection antigen expressed by UV-2240 was found on the plasma membrane, and unlike the previously characterized antigen of UV-1591, the UV-2240 antigen was removed by using the noncytolytic butanol extraction technique. The tumor antigen activity in butanol extracts was resistant to digestion by endoglycosidase F and alpha-mannosidase, but was destroyed by pronase. In addition, the immunoprotective activity in extracts of UV-2240 was thermostable. These data demonstrate that the UV-2240-specific tumor antigen possesses physicochemical properties distinct from those of its well-characterized counterpart UV-1591.

1-Butanol↗
PubMed1988

Incidence of cutaneous melanoma in the United States by histology with special reference to the face.

Cutaneous melanoma has been classified into three distinct histological subtypes based on histopathological and clinical features. The incidence of the least common type, lentigo maligna melanoma, has been most strongly associated with chronic sunlight exposure as its cause, especially lesions presenting on the face area. The relationship of sunlight exposure to the other two major subtypes, superficial spreading melanoma and nodular melanoma, is unclear. Based on over 13,000 cases of cutaneous melanoma collected by the Surveillance, Epidemiology, and End Results (SEER) program of the NCI, we report histological-specific incidence rates within four major anatomic sites: face, trunk, arm and shoulder, and leg and hip. The anatomic distribution for all histologies combined was the same as often reported with a male preponderance of melanomas on the face and trunk and female preponderance on the arm and leg. Age-specific incidence for melanoma of the face increased steadily with age in both genders, whereas it did not for the other three sites. The nine SEER areas were divided into North, Central, and South based on the UV index for each area. For melanomas of the face, lentigo maligna melanoma was higher in the Central and South than the North for both genders and increased with age. For superficial spreading melanoma, the pattern of occurrence was different. Incidence was higher in the Central than the North and for males it increased with age. There was a smaller increase for females. This study documents the incidence of cutaneous melanoma by histological subtype within four anatomic sites. The different shapes of the age-incidence curves suggest that different histologies may react differently to sunlight exposure as an etiological factor. Our findings strongly support the importance of considering histological subtypes of cutaneous melanoma in future etiological studies.

Adult↗
PubMed1988

Immunoregulation of carcinogenesis: past, present, and future.

Twenty years ago the concept that immunological mechanisms might regulate carcinogenesis was highly controversial. Today this concept survives in modified form and continues to evolve as our knowledge of the immune system, the etiology of cancer, and tumor antigens expands. This review illustrates how our ideas about immune surveillance have changed in recent years and considers the significance of these changes for the future directions of cancer immunobiology.

Animals↗
PubMed1988

Effect of ultraviolet-B radiation on the in vivo growth of murine melanoma cells.

The role of UV radiation in the development of malignant melanoma has yet to be clearly defined. The purpose of these studies was to determine whether UV irradiation of mice produces local or systemic alterations that increase the in vivo growth of transplanted melanoma cells. K-1735 melanoma cells were injected into the external ears of syngeneic C3H mice. UV irradiation of the mice before or at the time of injection of the melanoma cells accelerated the appearance of the tumors. The effect was observed when melanoma cells were transplanted directly into the site of UV irradiation, but not when they were injected into an unirradiated site. The initial survival of radiolabeled melanoma cells at the site of inoculation was not altered by UV irradiation of the host, suggesting that the accelerated appearance of tumors was due to an increase in the clonogenic potential of cells injected into UV-irradiated skin. The effect of UV irradiation on the development of other syngeneic tumors was also investigated. The outgrowth of a second melanoma was also accelerated in UV-irradiated mice, whereas the growth of a UV-induced fibrosarcoma, a methylcholanthrene-induced fibrosarcoma, and a spontaneous hepatocarcinoma was not affected. These results suggest that, in addition to its carcinogenic activity, UV radiation may contribute to the incidence of cutaneous melanoma because of a local effect on the skin that stimulates melanoma development.

Animals↗
PubMed1988

Role of helper T-lymphocytes in rejection of UV-induced murine skin cancers.

The purpose of this study was to examine the role of helper T-lymphocytes (Th) in the immunological rejection of UV-induced tumors. Mice repeatedly exposed to UV radiation develop suppressor T-lymphocytes that facilitate the growth of UV-induced tumors by interfering with host immunity. These suppressor cells specifically blocked the generation of antitumor Th, suggesting that Th may be important in the immunological rejection of UV-induced tumors. The Th activity generated by a UV-induced tumor that grows progressively in normal mice was compared with that generated by a highly antigenic, regressor clone of the same tumor. The regressing tumor cell line generated a much higher amount of Th activity than the parental, progressor tumor cell line. The amount of Th activity generated by a highly antigenic, UV-induced tumor injected into normal mice, in which it regresses, was compared to the Th activity in UV-irradiated mice, in which the tumor grows progressively. Again, tumor regression was associated with a higher amount of Th activity, and this increased activity was detectable in the environment of the regressing tumor. Lyt-1+ cells containing Th activity mediated the regression of a UV-induced tumor when injected with the tumor cells s.c. into immunosuppressed mice. Lyt-1- cells were cytotoxic to tumor cells in vitro but were unable to cause tumor rejection in vivo. These studies suggest that Th play a central role in the immunological rejection of UV-induced tumors.

Animals↗
PubMed1988

Proportion of antigenic variants induced by in vitro UV irradiation differs in clones derived from a single tumor.

The purpose of this study was to examine the capacity of different clones derived from the same tumor to generate highly antigenic cells after in vitro exposure to UV radiation. Cells from the metastatic murine melanoma K1735 and clones of K1735 differing in metastatic potential were exposed to UV radiation in vitro, cloned, and tested for antigenic properties in vivo. Approximately half of the clones isolated after UV irradiation of parental K1735 melanoma cells were highly antigenic (five of nine). Similar treatment of cells of a nonmetastatic clone of K1735 generated clones that were all antigenic (nine of nine). In contrast, only one of nine clones derived from UV-irradiated cells of a highly metastatic clone of K1735 were antigenic. Clones derived from unirradiated cultures were not antigenic variants. The increased antigenicity of cells derived from UV-irradiated cultures did not correlate with an increase in expression of cell surface class I major histocompatibility complex antigens. These results demonstrate that the frequency of antigenic variant production after UV irradiation is an intrinsic property of the particular cell line used, and that even cloned cell lines derived from a single tumor differ in their ability to generate antigenic variants after UV irradiation. In addition, they indicate that the increased antigenicity is not necessarily due to a UV-induced increase in expression of cell surface class I histocompatibility antigens.

Animals↗
PubMed1988

In vitro cytotoxic activity of interleukin 2-dependent murine Thy-1+ dendritic epidermal cell lines.

Thy-1+ dendritic epidermal cells (Tdec) are bone marrow-derived cells of T-cell lineage. In order to investigate the function of these cells, two interleukin 2-dependent Tdec lines (AU4 and AU16) were established from ear skin of C3H/HeN (MTV-) mice and examined for cytotoxicity against various murine tumor cells. The original phenotype of the Tdec, Thy-1+, AsGM1+, T3+, Lyt-1-, Lyt-2-, Lyt-5+, and L3T4-, was maintained in the cell lines. The Tdec cell lines (AU4 and AU16) lysed a wide spectrum of tumor cell lines in a 4-hr 51Cr-release assay. AU16 was more effective in killing a syngeneic UV-induced skin tumor (UV-2240) and an allogeneic, natural killer cell-resistant tumor (EL-4) than the YAC-1 cell line, which is highly sensitive to natural killer cells. Neither syngeneic nor allogeneic lymphoblasts were killed by AU16. Cytotoxicity was blocked by fixation of AU16 with paraformaldehyde but not by pretreatment of the cells with puromycin or mitomycin C. The finding that two Thy-1+ cell lines derived independently from murine epidermis have unique cytotoxic activity against murine tumor cells suggests that Tdec could play a role in local immune surveillance against skin cancers.

Animals↗
PubMed1988

Alterations in Langerhans cells during growth of transplantable murine tumors.

To investigate the response of Langerhans cells to tumor growth, we examined the appearance and number of ATPase+ and Ia+ dendritic cells in the epidermis covering subcutaneous tumors. Mice were injected with cells from syngeneic UVB- and PUVA-induced tumors and a melanoma, and the overlying skin was examined at various times during progressive tumor growth. An increase in the number of ATPase+ and Ia+ dendritic cells was observed in skin over all three tumor types. Morphologic alterations in the cells were also noted, including a decrease in dendricity. These changes were apparent only in skin directly over growing tumor masses; contralateral and perilesional skin was unaffected. Injection of nontumorigenic cells and implantation of silicon did not induce changes in Langerhans cells. Regression of highly antigenic tumor cells and tumor regression in immunized mice were not accompanied by detectable alterations in Langerhans cells, whereas changes in Langerhans cells were apparent during tumor growth in nude mice. These results demonstrate that changes in the number and morphology of Langerhans cells occur in response to tumor growth but that the changes are not dependent on immunologic or inflammatory responses.

Adenosine Triphosphatases↗
PubMed1988

Impact of ozone depletion on skin cancers.

Because of recent growth in the uses and production of certain chlorofluorocarbon compounds, the ozone layer is at risk of diminishing. The major effect of a decrease in ozone will be an increase in the amount of UV-B radiation in sunlight. Even a small increase in UV-B radiation will almost certainly affect human health. The most obvious effect of increased UV-B radiation will be an increase in the incidence of basal and squamous cell carcinomas. Other possible effects include a contribution to the development of cutaneous melanoma, ocular changes leading to the formation of cataracts, and immunologic perturbations.

Animals↗
PubMed1987

Effector and suppressor circuits of the immune response are activated in vivo by different mechanisms.

The application of fluorescein isothiocyanate (FITC) onto the skin of mice induces a contact hypersensitivity immune response. Lymph nodes draining the skin painted with FITC contain fluorescent cells that induce contact hypersensitivity to FITC when injected into normal mice. The antigen-presenting cells responsible for activating the effector pathway of the contact hypersensitivity response express Ia histocompatibility determinants and are resistant to inactivation with gamma-radiation. Exposing the skin to low doses of UV radiation (280-320 nm) before the application of FITC suppresses the contact hypersensitivity response to FITC. Cells present in the draining lymph nodes of these mice induce suppressor T lymphocytes when injected into normal recipients. The inducer cells in the draining lymph nodes are Thy 1+, Ia- and are inactivated by gamma-radiation. These studies demonstrate that different mechanisms are involved in the in vivo activation of effector and suppressor immune responses, and they suggest that the mode of initial antigen presentation determines which immunologic circuit will be activated in response to a contact-sensitizing antigen.

Adenosine Triphosphatases↗
PubMed1987

Perturbation of epidermal Langerhans cells in basal cell carcinomas.

Epidermal Langerhans cells (LC) play a pivotal role in a variety of local immune responses. Using ATPase-stained preparations, we evaluated the density and morphologic features of these cells in the skin of 12 patients with basal cell carcinoma (BCC). In three patients, we compared the density of LC in the tumor to that in the perilesional skin. In these cases, there was no difference in the numbers of LC/mm2 in the two sites. Perturbations of ATPase-positive, dendritic LC were evident in all specimens. These perturbations included various degrees of disruption of the usually uniform LC network and alterations in the morphology of LC. Many LC had rounded, deformed cell bodies, dendrites that were shortened or completely absent, and variations in the intensity of ATPase staining. With the use of an image analyzer, a measure of the deviation from circularity--a "dendricity index" (DI)--was obtained, based on the area and perimeter of the LC. A significantly lower DI, implying a predominance of less dendritic, more rounded LC, was observed in LC at the BCC surface than in LC present in perilesional skin. This finding raises the possibility that BCC may arise in areas where the morphology, or activity, of these immune cells has been altered; alternatively, the perturbations could reflect an effect of the tumor cells on LC morphology.

Adenosine Triphosphatases↗
PubMed1987

Ultraviolet carcinogenesis in athymic nude mice.

We have investigated the development of skin cancer from exposure to ultraviolet (UV) radiation in C3H- nu/nu nude mice. Nude mice, nude mice reconstituted with thymuses, and nude mouse skin grafted onto normal haired mice had similar tumor incidences and rates of tumor development. All tumors were squamous cell carcinomas and both well-differentiated and poorly differentiated lesions occurred in each of the groups. Transplants of the tumors that developed in nude skin grew preferentially in immunosuppressed mice as compared with normal mice, indicating that tumors from each treatment group were antigenic. These results indicate that the presence or absence of a functioning thymus does not seem to influence UV carcinogenesis.

Animals↗
PubMed1986

Regulation of the immune response against UV-induced skin cancers: specificity of helper cells and their susceptibility to UV-induced suppressor cells.

The purpose of this study was to determine the role of T helper (Th) cells in the immune response to UV-induced tumors. Repeated exposure of mice to UV radiation results in the production of suppressor T lymphocytes that facilitate tumor growth by inhibiting host immunity. To investigate whether the suppressor T cells inhibit the response to UV tumors by blocking the generation of Th, we employed an indirect method for measuring helper cell activity. We found that Th were produced in normal mice after immunization with UV-induced tumors. These Th appeared to be specific for the immunizing tumors, in contrast to the UV-induced suppressor cells, which recognize UV-induced tumors as a group. The suppressor T cells responsible for inhibiting tumor rejection have no effect on tumor-specific helper cell activity in vitro. However, UV-induced suppressor T cells transferred into unirradiated mice seem to block the generation of helper cell activity after immunization with UV-produced tumors. These results suggest the UV-induced suppressor cells may prevent tumor rejection by blocking the generation of Th.

Animals↗
PubMed1986

Stepwise immunologic selection of antigenic variants during tumor growth.

Using tumor-specific effector cells as probes, we have studied the immunologic changes that occur in tumor cells during continuous growth in a host. As a model, we used a highly immunogenic ultraviolet light (UV)-induced tumor that is rejected regularly by normal mice but grows progressively when transplanted into UV-irradiated mice. The immunogenic tumor growing continuously in these partially immunocompromised mice gave rise to genetically stable progressor variants that were poorly immunogenic. A sequence of changes in susceptibility to activated macrophages and tumor-specific cytolytic T cells was observed when serial reisolates from the continuously growing tumors were analyzed. First, the tumor cells developed resistance to the cytocidal effects of activated macrophages. This was followed by the loss of one and then a second tumor-specific antigen defined by syngeneic cytolytic T cells. The phenotypes of the developing antigen loss variants and their sequence of appearance were the same in several independent experiments, and the process was apparently determined by a hierarchy of the host's immune response to multiple independent tumor-specific antigens expressed by a single malignant cell. Our ability to generate the predicted variants in vitro before they actually appear in vivo suggests a possible approach to preventing the outgrowth of such immunoselected variants from a tumor.

Animals↗
PubMed1986

Generation of tumor-specific transplantation antigens by UV radiation can occur independently of neoplastic transformation.

The purpose of this study was to determine whether the UV-associated antigens present on tumors induced in mice by chronic UV irradiation could be induced by in vitro irradiation of cells that were already tumorigenic, or whether their occurrence was associated with the primary neoplastic transformation event. Cells of a nonantigenic, spontaneous fibrosarcoma cell line were exposed to UV radiation in vitro, were cloned, and were tested for antigenic properties. A large number of the clones obtained after UV irradiation of the fibrosarcoma cells were highly antigenic (20 of 39), whereas clones derived from unirradiated cultures were not (0 of 10). The antigenic variants did not induce cross-protection among themselves, but induced only variant-specific immunity in vivo. Several antigenic variants were tested for susceptibility to the action of UV-induced suppressor cells, which seem to recognize a common determinant shared among UV-induced tumors. The variants tested were indeed subject to the activity of the UV-induced suppressor lymphocytes. These results demonstrate that the unique antigenic properties exhibited by UV-induced murine skin cancers are also exhibited by cells exposed to UV radiation in vitro. In addition, they imply that the UV-associated antigens arise as a consequence of exposing cells to UV radiation and that they can occur independently of an initial neoplastic transformation event.

Animals↗