Search results for "Transformation"
showing 10 items of 1634 documents
Biological activation of 1,3-butadiene to vinyl oxirane by rat liver microsomes and expiration of the reactive metabolite by exposed rats.
1983
When 1,3-butadiene is incubated with rat liver microsomes and NADPH both enantiomers of vinyl oxirane are formed, the amount of epoxide being dependent on incubation time, microsomal protein, and substrate concentration. Inhibition by SKF 525 A or dithiocarb as well as induction by pretreatment with phenobarbital or 20-methylcholanthrene suggest participation of cytochrome P-450 in this reaction. The amount of epoxide is enhanced by addition of 1,1,1-trichloropropene oxide and reduced by glutathione, especially in the presence of hepatic cytosol. When rats are exposed to 1,3-butadiene in a closed chamber (conditions of maximal metabolism) vinyl oxirane is exhaled and can be quantitatively d…
USE OF FUZZY NEURAL NETWORKS IN MODELING RELATIONSHIPS OF HPV INFECTION WITH APOPTOTIC AND PROLIFERATION MARKERS IN POTENTIALLY MALIGNANT ORAL LESIONS
2005
To evaluate in oral leukoplakia the relationship between HPV infection and markers of apoptosis (bcl-2, survivin) and proliferation (PCNA), also conditionally to age, gender, smoking and drinking habits of patients, by means of Fuzzy neural networks (FNN) system 21 cases of oral leukopakia, clinically and histologically diagnosed, were examined for HPV DNA presence, bcl-2, survivin and PCNA expression. HPV DNA was investigated in exfoliated oral mucosa cells by nested PCR (nPCR: MY09-MY11/GP5-GP6), and the HPV genotype determined by direct DNA sequencing. All markers were investigated by means of standardised immunohistochemistry procedure. Data were analysed by chi-square test, crude OR an…
Malignantly transformed non-parenchymal liver epithelial cells and transformed oval cells suppress the homotypical gap junctional intercellular commu…
1995
Isolated rat liver parenchymal cells (PC) were co-cultured with a non-parenchymal rat liver epithelial cell line (NEC) or with an oval cell line. The homotypical gap junctional intercellular communication (GJIC) between the liver PC was measured after microinjection of Lucifer Yellow by dye transfer. The rat liver PC were dye coupled between 87% and 100% for at least 1 week in both co-cultures, in contrast to PC In monoculture between which no dye coupling was left after 1 week. When liver PC were co-cultured with a transformed and tumorigenic NEC or with a transformed and tumorigenic oval cell line the homotypical GJIC between the liver PC was drastically decreased with culture time, and t…
HPV DNA and survivin expression in epithelial oral carcinogenesis: a relationship?
2004
Abstract HPV has been thought to be involved in the development of several oral diseases, such as premalignant mucosal lesions and oral carcinoma. Survivin is a recently characterized IAP protein, which is abundantly expressed in most solid and haematological malignancies, but undetectable in normal adult tissues. Aim of this study was to investigate survivin expression and HPV presence in oral premalignant lesions and oral carcinoma. 47 samples of oral tissue including 11 squamous cell carcinomas (OSCC), 16 oral leukoplakias (OL) and 20 normal oral mucosa specimens, after investigation of HPV presence by nested PCR (consensus MY/GP primers) and viral genotype identification by direct seque…
cAMP-dependent phosphorylation of CYP2B1 as a functional switch for cyclophosphamide activation and its hormonal controlin vitro andin vivo
2001
An important feature of cytochrome P450 (CYP) 2B1 is its high ability to convert the prodrug cyclophosphamide (CPA) to therapeutically cytotoxic metabolites, resulting in interstrand DNA-cross-linking and cell death. We have examined whether and how the phosphorylation of CYP2B1 influences CPA metabolic activation in vitro and in vivo. We found first that only part of the total CYP2B1 pool undergoes phosphorylation. This part is fully inactivated. Second, phosphorylation of CYP2B1 in intact hepatocytes reduced by up to 75% toxification of CPA to mutagenic metabolites (totally dependent on the same preferentially CYP2B-catalyzed 4-hydroxylation of CPA as is the generation of highly cytotoxic…
Prostate cancer: from the pathophysiologic implications of some genetic risk factors to translation in personalized cancer treatments.
2013
Several pathologies affect human prostate, such as prostate cancer (PC), which is the most common non-skin malignant cancer in Western male populations. A complex interaction between genetic and environmental factors (i.e. infectious agents, dietary carcinogens) and hormonal imbalances has been reported to have a fundamental role in PC pathophysiology by evoking chronic inflammation. Thus, chronic inflammation drives prostate carcinogenesis and neoplastic progression. No adequate biomarkers exist until now to guide PC prognosis and treatment. Accordingly, the research has particularly focused its attention on genetic variants in genes, codifying molecules of signaling innate immune/inflamma…
Characterization of highly polar bis-dihydrodiol epoxide--DNA adducts formed after metabolic activation of dibenz[a,h]anthracene.
1993
Dibenz[a,h]anthracene as well as a biologically important metabolite of dibenz[a,h]anthracene, namely the M-region dihydrodiol trans-3,4-dihydroxy-3,4-dihydrodibenz[a,h]anthracene were in addition to further metabolism to a bay region diol epoxide, extensively transformed to a distal bisdihydrodiol, 3,4,10,11-tetrahydroxy-3,4,10,11-tetrahydro-dibenz[a,h]anthracene, which exhibited after renewed metabolic activation high DNA binding efficiency, leading to a new class of very polar DNA adducts. After incubation of dibenz[a,h]anthracene with DNA in the presence of liver microsomes from Aroclor 1254 treated male Sprague-Dawley rats highly polar DNA adducts probably originating from 3R,4R,10R,11…
The value of immunohistochemical research on PCNA, p53 and heat shock proteins in prostate cancer management: a review.
2006
This review addresses the significance of the expression of proliferating cell nuclear antigen (PCNA), p53 and some heat shock proteins (Hsps) in prostate carcinoma (PC). In fact, PCNA and p53 are two widely discussed tools in PC diagno- sis, mainly because of the controversy regarding the signifi- cance of their expression during prostate cancer development and progression. At the same time, only few studies have shown the potential role of Hsps in carcinogenesis and their overexpression in pre-neoplastic and neoplastic lesions of the prostate. We briefly describe the physiological roles of Hsps in normal cells, and the significance of their immunohistochem- ical detection in PC as well as…
An experimental design for the controlled modulation of intracellular GSH levels in cultured hepatocytes
2006
This work proposes a practical experimental approach that allows the rapid in situ generation of a wide range of intracellular GSH concentrations in the intact hepatocyte under highly reproducible conditions. The strategy involves the use of diethyl maleate, a thiol-reactive electrophile that causes rapid and extensive GSH depletion, as well as GSH monoethylester, a GSH analogue that is readily taken up by cells and deesterified intracellularly to render GSH. For both agents, we have analyzed (i) the minimal exposure time required to produce a maximal and dose-related effect on intracellular GSH without altering hepatocyte viability or subsequent survival in culture, and (ii) the relative s…
Synthesis of fjord region tetraols and their use in hepatic biotransformation studies of dihydrodiols of benzo[c]chrysene, benzo[g]chrysene and diben…
1998
Metabolic activation of the racemic benzo[c]chrysene-trans-9,10-, benzo[g]chrysene-trans-11,12- and dibenzo[a,l]pyrene-trans-11,12-dihydrodiols to fjord region syn- and anti-dihydrodiol epoxides by microsomes of Aroclor 1254-treated Sprague-Dawley rats has been examined. Since the fjord region dihydrodiol epoxides were hydrolytically unstable under the experimental conditions, their enzymatic formation was determined by analyzing the tetraols as their products of acidic hydrolysis upon addition of perchloric acid. The various stereoisomeric tetraols formed were separated by HPLC and identified by co-chromatography with authentic tetraols, which had been prepared by acidic hydrolysis of synt…