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F Stenbäck

Publications and source records attributed to F Stenbäck.

141 records · Page 8Linked to original sources
PubMedDate not supplied

Immunohistochemical detection of human placental cytochrome P-450-associated mono-oxygenase system inducible by maternal cigarette smoking.

Several xenobiotic-metabolizing mono-oxygenase activities, in conjunction with the immunohistochemical localization of the respective cytochrome P-450 forms, were investigated in placentae from smoking and non-smoking women. The antibodies used in the immunohistochemical analyses were monoclonal antibodies (MAbs) 1-7-1 and 2-66-3, prepared against the 3-methylcholanthrene-induced and phenobarbital-induced rat liver P-450, respectively. The mono-oxygenase activities were higher in placental microsomes from smokers, although no difference was observed in microsomal P-450 content. A distinct positive staining with MAb 1-7-1 was detectable in the trophoblastic layer of all placentae from smokers. In placentae from non-smokers, minimal cytoplasmic staining was observed in large villi in a few trophoblastic cells. The staining reaction was negative when MAb 2-66-3 or non-specific antibody were used. These results demonstrate that maternal cigarette smoking induces in the trophoblastic layer of the placenta a cytochrome P-450 form which is detectable immunohistochemically with the monoclonal antibody to 3-methylcholanthrene-inducible P-450 in rat liver.

Antibodies, Monoclonal↗
PubMedDate not supplied

Collagen matrix in development and progression of experimentally induced respiratory neoplasms in the hamster.

Intratracheal instillations of 7H-dibenzo(c, g)carbazole (DBC), a tobacco smoke component, into Syrian golden hamsters, resulted in preneoplastic lesions and benign and malignant respiratory neoplasms. Neoplastic progression was associated with specific changes in the extracellular matrix (ECM), dependent on the stage of tumor development. DBC-induced tracheobronchial squamous metaplasia was associated with an increase in collagen type I and type III deposition in the subepithelial ECM, as observed by computer-assisted image analysis of immunohistochemical staining for the aminoterminal propeptides of collagen type I (PINP) and collagen type III (PIIINP). Increased collagen matrix synthesis was detected in dysplasia by in situ hybridization of alpha1(I) mRNA for collagen I and alpha1(III) mRNA for collagen type III after continued exposure to DBC. In well-differentiated squamous cell carcinomas with an expansive growth pattern, collagen deposition increased, as did fiber size. In moderately differentiated neoplasms, basement membrane (BM) destruction and invasion was associated with a destructive growth pattern and decreases in collagen synthesis and the deposition of new collagen. Preserved deposition of mature collagen was detected by staining for the telopeptide of collagen type I propeptide. In less differentiated tumors, ECM development was minimal, with few and small fibers, possibly explaining the rapid development of these neoplasms. Transforming growth factor beta (TGFbeta1) immunoreactivity was increased in hyperplastic epithelium and well differentiated neoplasms and decreased in dysplasia and less differentiated squamous cell carcinomas, while TGFbeta2 and TGFbeta3 expression was also distinct in neoplastic cells. Collagen synthesis and epithelial differentiation were associated with an increased number of myofibroblasts in the ECM and with increased TGFbeta3 immunoreactivity in differentiated cells and in the matrix. The nature of the composition of the ECM was related to neoplastic growth and progression when analyzed by computer-associated image analysis, revealing alterations in collagen structure, size, and shape.

Animals↗
PubMedDate not supplied

Sequential functional and morphological alterations during hepatocarcinogenesis induced in rats by feeding of a low dose of 2-acetylaminofluorene.

The early cellular events in liver carcinogenesis were studied in Fischer-344 male rats that either were fed 200 ppm 2-acetylaminofluorene (AAF) for up to 10 wk or were fed the carcinogen for 8 wk followed by maintenance for an additional 24 wk. By 1 wk of exposure, AAF caused a reduction in the number of glutamine synthetase (GS)-positive centrilobular hepatocytes, an increase in DNA synthesizing hepatocytes in the central areas of the hepatic lobules, and a shift from multinucleated to mononucleated hepatocytes, although overt hepatocellular necrosis was not evident. By 3 wk, altered hepatocellular foci characterized by deficiencies in iron storage (IS-) and collagen production and by expression of gamma-glutamyl transferase (GGT+) and placental-type glutathione transferase (PGT+) activity appeared. Single PGT+ cells were also found. During continued exposure, foci increased in number, size, and total area with the increases escalating between 8 and 10 wk of exposure. Cessation of AAF exposure at 8 wk resulted in a slight decrease in the number of foci after a further 6 wk of maintenance, but with continued maintenance for another 6 and 12 wk, the number again increased. IS- characterized the majority of foci during carcinogen administration, whereas after cessation of exposure, GGT+ and PGT+ foci predominated. None of the foci were positive for GS. After AAF exposure for 10 wk, a few neoplasms developed and greater numbers occurred after maintenance for a further 24 wk of rats exposed for 8 wk. We conclude the following: (a) the low dose of AAF caused subtle alterations in function and proliferation of normal hepatocytes and converted hepatocytes into focus cells; (b) reduction of the GS+ area is a sensitive indicator of cytotoxicity of AAF; (c) the development of some foci at an early stage depends on a promoting action of AAF, which ceased when the carcinogen was withdrawn, allowing some foci to undergo reversion; (d) a strong linkage exists in expression of IS-, GGT+, and PGT+ in foci; (e) the carcinogenic process accelerates in the absence of any indication of increased cytotoxicity by AAF; and (f) under the conditions of this study, no GS+ foci, adenomas, and carcinomas were found, indicating that no carcinogen-induced expression of GS occurred in these lesions and that GS expression is not linked to other phenotypic abnormalities.

2-Acetylaminofluorene↗
PubMedDate not supplied

Epidermal cell adhesion and basement membrane alterations in experimental skin tumour development.

BACKGROUND: Epidermal cell adhesion and basement membrane (BM) are essential for the differentiated structure of squamous epithelium, and both are reduced in malignant tumours. MATERIALS AND METHODS: We analysed the expression of cell adhesion-related proteins desmoplakin and E-cadherin, BM components laminin and collagen IV, and BM receptor integrin alpha 6 in experimental preneoplastic changes and neoplasms of skin. Different mouse strains (NMRI, C57Bl/6 and DBA/2) and exposure protocols (DMBA, UV, DMBA + UV) were used to find possible differences in the expression of cell adhesion and BM proteins within individual tumour types. RESULTS: The individual strain had an impressive role on the expression of tumors. The exposure model affected the type of tumour found and tumour behaviour. The location and expression of cell attachment proteins were dependent on morphology, but mouse strain and type of exposure had no effect. The decline in the expression of markers studied was gradual involving the cytoplasmic immunoreactivity of integrin alpha 6 and laminin observed in dysplastic epidermis, BM structure formation becoming increasingly disturbed in dysplasia; this was present in squamous cell carcinomas and absent in undifferentiated tumours. Desmoplakin expression gradually disappeared during the decline in differentiation. E-cadherin expression was preserved longer, and disappeared along with the loss of squamous properties. CONCLUSIONS: Desmoplakin and E-cadherin served in this study as differentiation markers. None of these proteins seem to explain the differences in the tumour sensitivity of individual mouse strains.

9,10-Dimethyl-1,2-benzanthracene↗