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Biomedical subjects

J Schweizer

Publications and source records attributed to J Schweizer.

At least 127 records · Page 7Linked to original sources
PubMed1982

Histological, proliferative, and biochemical alterations in dorsal epidermis of the Syrian golden hamster induced by 12-O-tetradecanoylphorbol-13-acetate and the calcium ionophore A 23187.

Long-term treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) of dorsal skin of 7,12-dimethylbenz(a)anthracene-initiated Syrian golden hamsters does not lead to the formation of epithelial tumors and leaves the epidermis essentially unchanged. However, previous histological studies by others have shown that hamster epidermis can be hyperplastically transformed by a single application of TPA but that the tissue is capable of gradually adapting to the drug after extended TPA exposure. We have investigated the response of hamster back epidermis to single and multiple treatments with increasing doses of TPA with regard to histological, proliferative, and biochemical alterations, and we show that in our animal strain the dorsal epidermis is resistant to even a single exposure to TPA, although the clearance rate of TPA is comparable to that in mouse epidermis and the metabolism of the substance is negligible. In contrast, the epidermis could be moderately stimulated by a single application of the nonpromoting calcium ionophore A 23187 and exhibited a strong proliferate and hyperplastic response following the simultaneous exposure to the calcium ionophore and TPA. Both types of hyperproliferation did not reveal an initial depression of the proliferative activity and were accompanied by typical alterations of the keratin polypeptide pattern, which was not detectable after treatment with TPA alone.

Adaptation, Physiological↗
PubMed1981

Diaplacental initiation of NMRI mice with 7,12-dimethylbenz[a]anthracene during gestation days 6--20 and postnatal treatment of the F1-generation with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate: tumor incidence in organs other than the skin.

The tumor spectrum and tumor incidence in organs other than the skin were investigated in the 12-O-tetradecanoylphorbol-13-acetate (TPA) treated F 1-generation of 13 groups of NMRI mice which had been initiated by a single intragastric dose of 7,12-dimethylbenz[a]anthracene during days 6, 8, and 10--20 of pregnancy. Promotion by topical application of TPA to the back skin was carried out twice per week 12 weeks after birth over a period of 26 weeks. The forestomach epithelium represented the only organ in which statistically significant 2-stage carcinogenesis could be demonstrated. A promotion effect could be seen in tumors of the Harderian gland, of the liver of male animals and on the development of both benign and malignant tumors of the lung in both sexes. Promotion treatment therefore led to an activation of initiated tumor cells in those organs in which a very sensitive, more or less narrowly spaced oncogenic determination period exists.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1981

Carcinoma-specific keratin polypeptide patterns in keratinizing epithelia of rodents : independence of species- and tissue-specific variations.

A comparative investigation of the one- and two-dimensional electrophoretic keratin polypeptide patterns of various keratinizing epithelial tissues and of benign and malignant tumors of these tissues in the rodent species mouse, rat and hamster was undertaken. Keratin polypeptides of all normal epithelia investigated (vaginal, anal and forestomach epithelium) appear in a molecular weight range of about 40 K--70 K daltons and can be divided according to molecular weight and electrical charge into three groups. The large keratins (group A) have a basic character, while the lower molecular weight components of groups B and C are acidic in nature. The tissue-specific variations within one species are minimal and, apart from minor quantitative differences, mainly concern differing numbers of components within groups A and B, whereas the species-specific variations are more pronounced and apply to all three groups of keratins, which show a variable number of individual polypeptides differing in molecular weights and/or electrical charge. Independent of the tissue- and species-specific differences, keratins of epithelial carcinomas exhibit a special pattern differing from that of their corresponding intact tissues, as well as from benign tumors, by the lact of the large keratin polypeptides of group A. These characteristic differences in the keratin polypeptide composition of normal epithelia and of benign and malignant tumors may be useful for the diagnosis of epithelial tumors.

Animals↗
PubMed1980

Langerhans' cell-free regions in orthokeratinizing sole-of-foot epidermis of the adult mouse.

The distribution of ATPase-positive Langerhans' cells was investigated in whole sheets of the glabrous sole-of-foot epidermis of the mouse. This completely orthokeratinizing tissue shows distinct morphological differences mainly with regard to the dermo-epidermal junction. Whereas the sharply outlined nodular prominences in the center of each footpad have a heavily undulated dermo-epidermal junction, the epidermal baseline in the surrounding tissue and the region just proximal to the footpad is flat. A dense population of evenly distributed ATPase-positive Langerhans' cells is found in the epidermis which surrounds the nodular structures. A slightly reduced population of Langerhans' cells is located in the epidermis of 80% of the nodules, occasionally showing a concentration in the pronounced epidermal ridges. Twenty percent of the nodules possess an epidermis which is completely free of Langerhans' cells. The results are discussed in view of the current hypothesis on the biological function of Langerhans' cells.

Adenosine Triphosphatases↗
PubMed1980

Two-stage skin carcinogenesis by systemic initiation of pregnant mice with 7,12-dimethylbenz(a)anthracene during gestation days 6-20 and postnatal promotion of the F 1-generation with the phorbol ester 12-tetradecanoylphorbol-13-acetate.

The DMBA-TPA-mediated two-stage skin carcinogenesis experiment was modified in that pregnant mice were systemically treated once during pregnancy with the carcinogen. Intragastric application times were fetal days 6, 8, and 10-20. A control group of pregnant mice received repeated doses (from days 8-20) of sesame oil, which was used as a solvent for DMBA. At the age of 12 weeks, the offspring of the control group were divided into two groups, one of which was left completely untreated, the other received TPA applications over 26 weeks. The 12-week old F 1-progeny of each transplacentally initiated group was also divided into subgroups, which either received no further treatment (subgroups A) or were promoted with TPA (subgroups B). Neither the F 1-animals of the two control groups nor that of the transplacentally initiated but postnatally not promoted subgroups 6 A-20 A developed skin tumors. The same holds true for the TPA-promoted offsprings of mother animals which had received DMBA at days 6 and 8 of gestation. Skin tumor development after TPA promotion was first observed in animals of subgroup 10 B. Thereafter, tumor rates and tumor yields increased and latency periods decreased progressively in the B-subgroups with the postponement of initiation to later fetal periods. Day 19 of prenatal development proved to be the most sensitive period to transplacental initiation, whereas initiation at day 20 led to a significant decrease in tumor rate and yield. The capability to initiate skin tumors and the extent of initiation can be correlated to both the organogenesis of the epidermis and its proliferative rate in utero.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1980

Keratins as markers of malignancy in mouse epidermal tumors.

A comparative study of the keratin composition of adult and neonatal mouse epidermis, benign and malignant tumors of mouse skin and murine epidermal cells grown in culture revealed striking differences in the keratin polypeptide patterns when analyzed by one-dimensional gel electrophoresis. Not only did the study confirm body-site specific alterations in the keratin patterns within one species, but it also demonstrated that similar to cultured epidermal cells, three malignant skin tumors investigated specifically lacked a group of keratin components with molecular weights larger than 61,000 daltons, which were invariably present in all normal and also in benign tissues. These findings offer the possibility of using keratins as molecular markers of the malignant state of epidermal cells. Two-dimensional gels of the keratin polypeptides of normal epidermis and of benign tumors exhibited spot patterns which could be divided at the 61,000 dalton level into an essentially basic subgroup, comprising the high molecular weight keratins, and an acidic subgroup including the low molecular weight components. The two uppermost proteins of cultured epidermal cells and carcinomas (molecular weights 61,000 and 58,000 daltons) belong to the acidic subgroup in normal tissues as well as in papillomas. However, in the case of malignant tumors and in vitro transformed epidermal cells they showed distinct alterations in charge in that they migrated into the more alkaline part of the gel. The number of spots appearing in the more basic region of the gel could be inversely related to the degree of differentiation exhibited by tumors or in vitro cells.

Animals↗
PubMed1980

Synthesis in vitro of keratin polypeptides directed by mRNA isolated from newborn and adult mouse epidermis.

A method is described which allows the isolation of undegraded total cellular RNA from living epidermis in a one-step procedure. Epidermal tissue is homogenized in 4 M guanidinium thiocyanate/2% sarkosyl buffer and centrifuged through a 5.7 M CsCl cushion. Under appropriate density conditions in the homogenate, large amounts of RNA are sedimented free of DNA and protein to the bottom of the tubes. A prerequisite for the applicability of this method is the preparation of pure epidermis under conditions which efficiently inactivate endogenous RNases. Oligo(dT) affinity chromatography of total RNA yields 3-4% of polyadenylated RNA. Translation of poly(A)-rich fractions from both newborn and adult mouse epidermis in a cell-free reticulocyte system leads to the synthesis of proteins with electrophoretic mobilities identical to those of native keratin polypeptides of the corresponding tissue. Similar to native keratin polypeptides, these proteins are highly insoluble and can selectively be enriched by high-salt extraction of the translation assays. The CNBr cleavage pattern of these purified proteins is identical to that of native keratins. There is no evidence for the synthesis of precursors of these proteins.

Aging↗
PubMed1979

Neogenesis of functional hair follicles in adult mouse skin selectively induced by tumour-promoting phorbol esters.

Neogenesis of functional hair follicles in the tail skin of adult mice can quantitatively be demonstrated after long-term treatment with tumour-promoting phorbol esters. The ability to induce the formation of new hair follicles correlates with the hyperplasiogenic and tumour-promoting capacity of the phorbol esters. Hyperplasiogenic but nonpromoting phorbol esters do not lead to the formation of new hair follicles.

Animals↗
PubMed1979

Systemic two-stage carcinogenesis in the epithelium of the forestomach of mice using 7,12-dimethylbenz(a)anthracene as initiator and the phorbol ester 12-O-tetradecanoylphorbol-13-acetate as promoter.

In a modified two-stage carcinogenesis experiment, the effectiveness of the initiator 7,12-dimethylbenz(a)anthracene (DMBA) and the tumor-promoting phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) in the epithelium of the forestomach of the mouse has been investigated. Fifty mice were treated intragastrically with a single dose of DMBA (50 mg/kg body weight), followed by repeated intragastric administration of TPA (10 mg/kg body weight) over a period of 35 weeks. In comparison with the corresponding control groups (no treatment, DMBA initiation only, and TPA treatment only), the initiated and promoted group clearly showed the highest tumor incidence in the target organ (45 tumor-bearing animals of 50 animals). No tumors of the forestomach were found in the untreated control group and the TPA-treated group, whereas in the DMBA-initiated group, ten animals had developed tumors of the forestomach. In addition to the mouse skin model for two-stage carcinogenesis, the mouse forestomach appears to respond to DMBA initiation-TPA promotion. This organ provides an additional tissue with which to investigate tumor promotion and further to ascertain specific parameters of the promotion step.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1978

Transmaternal modification of the Berenblum/Mottram experiment in mice.

The classical 2-stage carcinogenesis experiment has been modified in that the carcinogen DMBA was applied to pregnant mother animals at different dose levels and different time intervals during pregnancy. Promotion with the phorbol ester TPA was performed as usual by application of the promoter on the back skin of mice of the F-1 generation. It can be shown that it is possible to initiate fetal epidermal cells by transmaternal route and to promote them to produce visible skin tumors post natum. Tumor promotion by TPA is not restricted to the epidermis, since a broad spectrum of tumors of internal organs can be demonstrated in the initiated and promoted animals. This more general promoting activity of TPA--which implies its absorption and distribution throughout the whole body--has not yet been described. In addition, especially sensitive phases during fetal life with regard to initiation of cells by the carcinogen can be demonstrated. These phases comprise the last third of pregnancy and coincide with a high proliferative activity and the onset of differentiation of the fetal epidermis. The results emphasize the important role of prenatal carcinogenesis and demonstrate the increased risk also to the human organism by either prenatal initiation or postnatal promotion.

9,10-Dimethyl-1,2-benzanthracene↗