Biomedical subjects

U Mohr

Publications and source records attributed to U Mohr.

At least 73 records · Page 4Linked to original sources

PubMed1993

Morphology and histogenesis of squamous cell metaplasia of the rat lung after chronic exposure to a pyrolized pitch condensate and/or carbon black, or to combinations of pyrolized pitch condensate, carbon black and irritant gases.

Female Wistar rats were exposed to different concentrations of a pyrolized pitch condensate and/or carbon black particles and/or a combination of irritant gases for 18 hours/day, 5 days/week for 10 months, followed by a clean air period of up to 20 months. Bronchiolo-alveolar hyperplasia and squamous metaplasia were important components of the resulting lesions. Squamous metaplasia and associated hyperplasia was investigated by routine histology, scanning and transmission electron microscopy, and by immunohistochemical detection of various cytokeratins (CKs). Intensely CK positive squamous metaplasia lacking a distinct stratum spinosum was distinguishable from squamous metaplasia with a distinct stratum spinosum that reacted weakly CK positive or CK negative. The CK positive type was histologically characterized by narrow intercellular spaces, the weakly CK positive or CK negative type had markedly enlarged intercellular spaces. Differentiated hyperplastic epithelium and the normal lung parenchyma reacted CK negative. In poorly differentiated hyperplasia of the alveolar type associated with squamous metaplasia scattered cells with characteristics of squamous differentiation were detected. Ultrastructurally these cells showed increased amounts of filament bundles and immunohistochemically a positive reaction with the CK antibody. These cells were regarded as precursor stages of squamous metaplasia of the lung periphery in rats.

Animals↗

PubMed1993

Frequency of metastasis depending on histologic type of primary lung carcinoma in rats.

A total of 123 malignant lung tumors (97 adenocarcinomas, 23 adenosquamous carcinomas and 3 squamous cell carcinomas) were induced in Han:WIST rats by 25 weekly subcutaneous injections of dipentylnitrosamine (DPNA). 43% of these adenocarcinomas and 87% of the adenosquamous carcinomas metastasized into various organs. The three squamous cell carcinomas showed no metastatic spread. More than half (65%) of the metastases from the adenosquamous carcinomas were composed of adenocarcinomatous components alone. Thus, the general acceptance in humans that pulmonary adenocarcinomas tend to metastasize more frequently than squamous cell carcinomas was proved in experimental animals.

Adenocarcinoma↗

PubMed1993

Intracranial metastases of induced lung carcinomas in rats.

Through 25 weekly subcutaneous injections of dipentylnitrosamine (DPNA), metastasizing lung carcinomas were induced in 56 Hann: Wistar rats. Among them nine animals had intracranial metastases. Four metastases were localized in the pituitary, three in the choroid plexus of the IIIrd ventricle, one in the choroid plexus of the IVth ventricle, and one in the brain-stem. Thus, the preferential sites of intracranial metastasis were the choroid plexus of the ventricles and the pituitary. No metastatic spread was found in the cerebral hemisphere. Five of the metastatic tumours resembled the primary pulmonary adenocarcinoma. In the other four, the primary was an adenosquamous carcinoma but only adenocarcinomatous components were present in the metastasis.

Adenocarcinoma↗

PubMed1992

Metastasizing lung carcinomas in Hann: Wistar rats.

In Hann:Wistar rats, 25 weekly subcutaneous injections of dipentylnitrosamine (DPNA) at doses of 0, 62.5, 125 and 250 mg/kg body weight induced lung carcinomas which metastasized partly. The incidence of the primaries was 2.5, 20.0, 77.5 and 100% in the males and 0, 0, 12.5 and 57.5% in the females, respectively. The frequency of metastases was 0, 12.5, 38.7 and 72.5% in the males and 0, 0, 40.0 and 52.2% in the females, respectively. The most common metastatic sites in males and females together were: lung-associated lymph nodes (82.1%), adrenal gland (53.6%), kidney (39.3%), pancreas (32.1%), bones (16.1%), heart (12.5%), mesentery (12.5%) and CNS (8.9%). In the females, metastases were also detected in the uterus (21.4%) and ovary (42.9%). The results indicate that: (1) through subcutaneous injections of DPNA metastasizing lung carcinomas can be induced with high incidence, and (2) the metastatic pattern is very similar to human cases. Thus, this model could be useful for the study of metastasizing lung carcinomas in experimental animals.

Adenocarcinoma↗

PubMed1992

The carcinogenic effect of 2,2-dioxopropylnitrosamine on the renal pelvic epithelium of Sprague-Dawley rats, after chronic subcutaneous injections.

The carcinogenicity of 2,2-dioxopropylnitrosamine on the urinary tract was investigated in three experimental groups of Sprague-Dawley rats (15 males, 15 females/group) by weekly subcutaneous administration for the life of the carcinogen at dose levels 1/5, 1/10 and 1/20 of the LD50, and compared with that in a similar group of untreated controls. It resulted in the induction of urinary tract tumours in 42 out of 79 effective animals (53%). Of these animals, 38 developed tumours within the renal pelvis. In the high-dose group, females had a 100% incidence of renal pelvic tumours, and males 73%. In all experimental groups, renal pelvic tumours were more frequent than ureteral and vesical ones. Histologically, the tumours were transitional cell papillomas and carcinomas, except for one squamous carcinoma. Out of 66 tumours, 42 (64%) were low-grade. High-grade tumours arose mainly in the renal pelvis of animals belonging to the highest-dose group. This experiment offers a useful model for the study of mechanisms involved in renal pelvic carcinogenesis.

Animals↗

PubMed1992

Atypical malignant mesotheliomas with osseous and cartilaginous differentiation after intraperitoneal injection of various types of mineral fibres in rats.

The histopathological appearance of malignant mesotheliomas with osseous and cartilaginous differentiation is described in detail. Bone and cartilage occurred in mixed and sarcomatoid mesotheliomas which were induced by intraperitoneal injection of various types of asbestos fibres (asbestos cement, crocidolite, UICC-amosite, UICC-chrysotile B, Calidria-chrysotile). Bone or cartilage were found in 32.7% of mixed mesothelioma and in 12.8% of sarcomatoid mesotheliomas.

Abdominal Neoplasms↗

PubMed1992

Cardiac metastases of induced lung carcinomas in rats.

A detailed study was made of seven cardiac metastases resulting from induced lung carcinomas. Fifty-six metastasizing lung carcinomas were found in Hann: Wistar rats as a result of subcutaneous injection of DPNA (dipentylnitrosamine). Of these 56, seven (12.5%) metastasized to the heart (three adenocarcinomas and four adenosquamous carcinomas). The metastatic tumors were located in the epicardium, myocardium, or endocardium, and their histologic appearance conformed to that of the primary lung carcinomas. The frequency of the cardiac metastasis and the preference of location within the heart were comparable with human cases.

Adenocarcinoma↗

PubMed1992

Cytokeratin filaments of the liver of BALB/c mice as a sensitive marker of liver damage. Computer-aided characterization with the image analysing system "IBAS".

The cytoskeleton forms a complex structural network which is of major importance for both structural integrity and physiologic functions of the cell. The aim of the present investigation was to investigate whether hepatotoxic effects of nitrosamine and colchicine can be detected through changes in the cytokeratin filament system which is an important component of the cytoskeleton. Groups of 10 male and 10 female newborn BALB/c mice were treated with either 25 micrograms dimethylnitrosamine (DMN) injected intraperitoneally on the day of birth; or with a daily subcutaneous injection of 0.12 micrograms/kg b.w. colchicine starting at ten weeks of age. A third group of mice served as untreated controls. All animals were held under standard laboratory conditions until necropsy at 16 weeks of age. The group injected with DMN received 0.05% phenobarbital with their drinking water after weaning. The histologic changes in the liver tissue were characterized by light microscopy. Changes of the cytokeratin filaments were visualized by the indirect immunofluorescent technique and quantified by using the image analysing system "IBAS". The cytokeratin filaments in the DMN group were markedly increased in amount and had a variety of morphological alterations. These effects could be measured quantitatively and did not indicate any sex-dependent behavior. The colchicine group did not display any structural changes in the cytokeratin filaments but sex-dependent changes in the amount of keratin material was revealed by image analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Actin Cytoskeleton↗

PubMed1992

RITA--Registry of Industrial Toxicology Animal-data--progress of the working group.

A data base for the collection of histopathological diagnoses of neoplastic and pre-neoplastic lesions and related data from control animals involved in long-term carcinogenicity or toxicity studies has been operated since 1988. Factors which may have an influence on the spontaneous tumor rate are integrated in the data base. Systematized nomenclature and standardized diagnostic criteria have been established as well as the applied data acquisition and data validation procedure.

Animals↗

PubMed1992

Effects of dipentylnitrosamine (DPNA) on the respiratory tract of rats.

Wistar rats (40 males and 40 females), treated over a period of 25 weeks with subcutaneous injections of dipentylnitrosamine (DPNA) at doses of 0, 62.5, 125 and 250 mg/kg body weight showed dose-dependent, sex-related, proliferative and metaplastic alterations in the upper and lower respiratory tract within one year. The biologic behavior of the induced lung tumors is very similar to that of human lung adenocarcinomas.

Adenocarcinoma↗

PubMed1992

Osteochondroma in laboratory rats: a report of 3 cases in a Fischer-344, a Sprague-Dawley, and a Wistar rat.

Three cases of osteochondroma in a male Sprague-Dawley (SD) rat, a female Fischer (F344) rat, and a male Wistar rat are described. The rats were aged between 26 and 30 months. All osteochondromas were considered to be of spontaneous origin. The Wistar rat had multiple osteochondromas on both hind legs, the skull base, and a lumbar vertebra, whereas each of the F344 and SD rats was affected by a solitary osteochondroma, also on a lumbar vertebra. The lumbar osteochondromas were similar in appearance in all rats and consisted of a central core of trabecular bone, interspersed with fatty marrow and covered by a cap of hyaline cartilage. The additional tumors in the Wistar rat represented different developmental stages of osteochondroma with or without endochondral activity. The osteochondromas in the rats were morphologically similar to those described in humans and some domestic animal species.

Animals↗

PubMed1992

Visual documentation of neoplasms as part of the REGISTRY Nomenclature Information System.

The REGISTRY Nomenclature Information system (RENI) is a program which runs on IBM-compatible personal computers. It includes internationally accepted diagnostic criteria for tumors and pre-neoplastic lesions in the rat to be used in toxicologic pathology. A video disk system, connected to the computer, provides colored pictures of histopathological reference slides, which are used for a visual documentation of the written criteria.

Animals↗

PubMed1991

Secretory differentiation and cell type identification of a human fetal bronchial epithelial cell line (HFBE).

A human fetal bronchial epithelial cell line (HFBE) grew in an undifferentiated pattern under conventional culture conditions. Despite a somewhat fibroblastic shape the cells maintained immunoreactivity to cytokeratin, carcinoembryonic antigen and epithelial membrane antigen. When grown on a collagen gel in a growth-hormone-supplemented medium, their spindle shape became more conspicuous. With an additional supplement of vitamin A (6 micrograms/ml), most of the cells underwent differentiation by producing many bright inclusion bodies which proved to be strongly positive with periodic acid-Schiff and weakly positive with alcian blue staining. Electron microscopy revealed a well-developed rough endoplasmic reticulum, an enlarged Golgi apparatus and many highly electron-dense secretory granules resembling those of Clara cells. Biochemical analysis demonstrated that HFBE cells cultured on collagen gel with vitamin A secreted hyaluronic acid and neutral glycoproteins containing mainly N-linked glycoproteins whose glycans were of a complex type. A monoclonal antibody (SEC-41) generated against the neutral glycoproteins detected a glycoprotein of approximately 52 kDa in the spent culture medium of differentiated HFBE cells. This antibody also reacted with the intracytoplasmic secretory granules in these cells. When tested on frozen sections of lung tissue, the immunohistochemical reactivity of the SEC-41 antibody was confined to Clara cells, some type II pneumocytes in the adult lung, and respiratory epithelial cells in the fetal lung. Moreover, this antibody could detect secretory glycoprotein in broncho-alveolar lavages from two patients. This paper clearly demonstrates that cells derived from human fetal bronchial epithelium can be cultivated in an undifferentiated precursor state and, under appropriate culture conditions, can be stimulated to undergo differentiation into a Clara cell type.

Bronchi↗

PubMed1991

Occurrence of sister-chromatid exchange and chromosomal aberration during vitamin A-induced cell differentiation in vitro.

Prompted by the recent growth in interest in the mechanisms of vitamin A (VA) action, we studied the effects of VA on the frequency of sister-chromatid exchange (SCE) and chromosome aberration (CA) in a culture system using a fetal Syrian hamster (female) pulmonary epithelial cell line (M3E3/C3). When manipulated by specific culture conditions, the cells in this system could be rendered competent for activation of polycyclic aromatic hydrocarbons. Cells induced to such a state were exposed to 0, 2, 8 and 24 micrograms/ml of VA for 4 days. The average frequency of SCE per metaphase increased from 1.64 at 0 micrograms/ml to 3.44 at 24 micrograms/ml with a moderate degree of dose dependence. In addition, the q-terminal area of X-chromosomes appears to be one of the most specifically vulnerable sites for SCE due to VA. The frequency of CA encompassing triradial, quadriradial, quinqueradial, ring and dicentric chromosomes also increased in a rather sigmoid fashion from 3.6% at 0 micrograms/ml to 14.8% at 24 micrograms/ml. Apart from the frequently demonstrated protective roles or otherwise less often encountered promotional effects of VA in the development of squamous metaplasia, neoplasia, neoplastic transformation or mutation, an alternative interpretation for the current results implies a possible relationship between SCE and CA caused by VA and cell differentiation and/or drug resistance mechanisms.

Animals↗

PubMed1991

Pulmonary response to toner upon chronic inhalation exposure in rats.

A chronic inhalation study of a test toner was conducted by exposure of groups of F-344 rats for 6 hr/day, 5 days/week for 24 months. The test toner was a special Xerox 9000 type xerographic toner, enriched in respirable-sized particles compared to commercial toner, such that it was about 35% respirable according to the ACGIH criteria. The target test aerosol exposure concentrations were 0, 1.0 (low), 4.0 (medium), and 16.0 (high) mg/m3. Titanium dioxide (5 mg/m3) and crystalline silicon dioxide (1 mg/m3), used as negative and positive controls for fibrogenicity, were also evaluated. Inhalation of the test toner or the control materials showed no signs of overt toxicity. Body weight, clinical chemistry values, food consumption, and organ weights were normal in the toner- and TiO2-exposed groups, except for a 40% increase in lung weight in the toner high-exposure group. All of the changes in the toner-exposed groups were restricted to the lungs or associated lymph nodes. A chronic inflammatory response was evident from the bronchoalveolar lavage parameters for the toner high-exposure group. The incidence of primary lung tumors was comparable among the three toner-exposed groups and the TiO2-exposed, and air-only controls, as well as consistent with historical background levels. A mild to moderate degree of lung fibrosis was observed in 92% of the rats in the toner high-exposure group, and a minimal to mild degree of fibrosis was noted in 22% of the animals in the toner middle-exposure group. The pulmonary changes in the toner high-exposure group were smaller in magnitude than those found in the crystalline silica-exposed group. The comparative fibrogenic potency of TiO2, toner, and SiO2 was estimated to be 1:5:418 using a dosimetric model and assuming a common mechanistic basis. There were no pulmonary changes of any type at the toner low-exposure level, which is most relevant in regard to potential human exposures. The lung alterations in the toner high-exposure group are interpreted in terms of "lung overloading," a generic response of the respiratory system to saturation of its detoxification capacity. The maximum tolerated dose (MTD) criterion was met at the toner high (16 mg/m3)-exposure level.

Administration, Inhalation↗

PubMed1991

Colon adenocarcinomas in European hamsters after application of N-nitroso-bis 2-oxypropyl-amine.

In the European hamster (EH) weekly subcutaneous (s.c.) injections of N-nitrosobis-(2-oxypropyl)-amine (BOP) (LD50, males: 174 mg/kg, body weight (b.w.), females: 118 mg/kg b.w.) induced adenocarcinomas of the colon in 77% (1/10 LD50), 70% (1/20 LD50) and 87% (1/40 LD50) of the treated animals (combined incidence for both sexes (c.i.)). Cholangiocellular carcinomas, the second most common type of tumor were produced in a dose-dependent manner. Furthermore tumors were found in the respiratory tract, urinary tract the integumentum system and the exocrine pancreas. The presented data show a difference between the BOP-induced tumor spectrum in European hamsters and that of Syrian hamsters [5,8,11]. The high incidence of colon adenocarcinomas may provide a further model of colon carcinogenesis.

Adenocarcinoma↗

PubMed1991

On the question of a carcinogenic action of cobalt-containing compounds.

After subcutaneous injections of doses of 5 x 2 and 1 x 10 mg cobalt (II) oxide/kg/week (total dose 1,000 mg/kg), respectively 5 out of 10 and 4 out of 10 rats in a lifetime study developed local malignant tumours (controls 0/10). After intraperitoneal injections of 3 x 200 mg cobalt (II) oxide/kg 14 out of 20 rats developed malignant intraperitoneal tumours (controls 1/20). With a Co/Al/Cr spinel the same treatment produced malignant intraperitoneal tumours in only 2 out of 20 rats. After intratracheal instillation of cobalt (II) oxide in single doses of 2 mg/kg (total dose 78 mg/kg) and 10 mg/kg (total dose 390 mg/kg) there were 2 benign pulmonary tumours among 100 rats in the low-dose group and 2 benign and 4 malignant pulmonary tumours among 100 rats in among 100 rats in the high-dose group. The Co/Al/Cr spinel was tested intratracheally only in the high dose (total dose 390 mg/kg); among the 100 rats this produced 3 malignant pulmonary tumours. Alternating intratracheal instillation of cobalt (II) oxide (total dose 470 mg/kg) and benzo[a]pyrene (total dose 200 mg/kg) led to 9 malignant pulmonary tumours in 20 rats, whereas benzo[a]pyrene alone caused only 1 malignant pulmonary tumour in 20 rats. The results suggest that cobalt (II) oxide (76.7% Co) has a weakly carcinogenic effect. The Co/Al/Cr spinel investigated is still less active, and even in very sensitive tests (i.p. and i.t. administration) shows no statistically significant carcinogenic effect. This smaller effect may possibly be explained by its lower cobalt content (24.0%) or its much lower solubility (only less than 10% of the solubility of CoO in 0.1 n HCl).

Animals↗

PubMed1991

Altered actin organization in an N-methyl-N'-nitro-N-nitrosoguanidine-transformed pulmonary epithelial cell line.

After in vitro-induced neoplastic transformation by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), altered actin organization in pulmonary epithelial cells was examined. A certain correlation was found between anchorage independency (AI), tumorigenicity in nude mice and altered actin organization. DNase I inhibition assay demonstrated significant loss of detergent-insoluble F-actin (stress fibers, p less than 0.02) and soluble F-actin (single filaments, p less than 0.0001) after AI transformation in comparison with untransformed cells, while the level of G-actin increased significantly (p less than 0.0001). At the same time, fluorescence and electron microscopy also revealed that after AI transformation there was a striking loss of stress fibers usually accompanied by reorganization of at least some of the lost stress fibers into F-actin aggregations. After s.c. implantation of AI-transformed cells into nude mice followed by recultivation of the developed tumors, DNase I-inhibition assay showed a significant increase (p less than 0.001) in the level of detergent-insoluble F-actin as compared with untransformed cells, but no significant difference in the amount of G-actin. However, most of this increased detergent-insoluble F-actin was in the form of aggregations as revealed by immunofluorescence and electron microscopy. This growth behaviour-dependent alteration in actin organization occurring after exposure to MNNG may be causally related to the progressive development of neoplastic phenotypes, although the biological significance of actin aggregation formation remains unclear. The results have also pointed out the importance of parallel investigations into both the biochemical and morphological statuses of actin, particularly when it may be regarded as an indicator of neoplastic transformation and malignancy.

Actins↗