Search PubMed⌕ Search

Biomedical subjects

R Montesano

Publications and source records attributed to R Montesano.

At least 271 records · Page 15Linked to original sources
PubMed1976

In vivo induction of tight junction proliferation in rat liver.

The chronic administration of phalloidin induces an extensive development of tight junctions between rat hepatocytes. The junctional strands lose their predominantly parallel orientation with respect to the canalicular lumen and extend abluminally in irregular patterns which cover large membrane areas at considerable distance from the bile canaliculi. These changes indicate both proliferation and provide further evidence that these junctions are not permanent differentiations of the cell membrane.

Animals↗
PubMed1976

Development of insulin and glucagon binding and the adenylate cyclase response in liver membranes of the prenatal, postnatal, and adult rat: evidence of glucagon "resistance".

Although plasma glucagon levels in the rat fetus are in the adult range, hepatic glycogen is present in far greater abundance in the fetus than in the adult. To explain this paradox, adenylate cyclase response to glucagon was studied in partially purified membranes of rat livers obtained throughout perinatal life and at 3 months of age. The adenylate cyclase response to glucagon (10(-9) M) was only 7% of the adult response at day 15 of fetal life and 20% on the 21st day. No until after the 30th day postpartum did not reach maturity. Yet, the adenylate cyclase response to stimulation by NaF was comparable to the adult response throughout fetal life. The binding of [125I]iodoglucagon (2 X 10(-9) M) by these membrane preparations was only 1% of the adult level at day 15 of fetal life and increased to 23% at the 21st day, and, like the adenylate cyclase response to glucagon, did not reach maturity until after the 30th day of postnatal life. In contrast, insulin binding on the 15th day of gestation was 11% of the adult level and on the 21st day 45% of the adult level, reaching adult levels by the 30th postnatal day. An increase in membrane-associated particles, reflecting intramembranous protein, was observed during prenatal life, but the mean particle number per mum2 reached adult levels on the 21st day of fetal life, indicating that subsequent changes in hormone binding were clearly independent of non-specific changes in the number of particles. The findings suggest that the fetal liver is less sensitive to glucagon action than the adult liver, and that this glucagon "resistance" is mediated by a reduced capacity of the hepatocyte to bind glucagon at a time when substantial binding of insulin is demonstrable. Selective discrimination against glucagon may be important in promoting the anabolic processes required for normal fetal development.

Adenylyl Cyclases↗
PubMed1976

Mutagenicity and metabolism of vinyl chloride and related compounds.

The various adverse biological effects of vinyl chloride appear to be dependent upon the metabolic conversion of this compound into chemically reactive metabolites. The metabolism of vinyl chloride in mammals and in man, including the formation of monochloroacetic acid and some identified sulfur conjugates is reviewed. Hepatic microsomal mixed function oxidases from rats, mice, and humans were equally effective in transforming vinyl chloride into alkylating agents in vitro. Two of the enzyme reaction products, i.e., chloroethylene oxide and 2-chloroacetaldehyde, showed potent genetic activity in microorganisms and Chinese hamster V79 cells. The role of liver microsomal enzymes in the generation of electrophilic mutagenic vinyl chloride metabolites is discussed.

Animals↗
PubMed1976

[Carcinogenicity of N-nitroso compounds].

The toxic, carcinogenic and mutagenic effects of N-nitroso compounds are briefly discussed with reference to recent reviews. These adverse biological effects are discussed in relation to the necessity of metabolic activation by microsomal enzymes for the nitrosamins but not for the nitrosamides.

Amides↗
PubMed1975

Production of epithelial and mesenchymal tumours with rat liver cells transformed in vitro.

Epithelial-like cells originating from the livers of 10-day and 8-week-old BD rats were established in culture. The cells were treated in vitro for 1 or 4 weeks with dimethylnitrosamine (DMN) or N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Although some structural changes were observed in treated cells, it was not possible to score for morphological transformation in vitro. Newborn syngeneic rats were injected with 1.5-2 times 10(6) treated or 1.5-5 times 10(6) control cells at various times up to 38 weeks from the beginning of treatment with the carcinogen. Following the injection of DMN-treated cells, a total of 32 of the 42 injected rat developed tumours, of which 17 were epithelial, 10 carcinosarcomas and 5 fibrosarcomas. Following the injection of the MNNG-treated cells into 61 rats, a total of 30 tumours were observed, including 8 carcinomas, 9 carcinosarcomas and 13 fibroscarcomas. Tumours, mainly of the mesenchymal type, were also observed in rats inoculated with control cells but at a lower frequency. The observation observed in rats inoculated with control cells but at a lower frequency. The observation of mesenchymal tumours is attributed to the presence of a mixed population of epithelial and mesenchymal cells in the orginal culture.

Animals↗
PubMed1975

Human, rat and mouse liver-mediated mutagenicity of vinyl chloride in S. typhimurium strains.

Exposure of S. typhimurium strains TA 1530, TA 1535 and G-46 to vinyl chloride increased the number of His+ revertants/plate 16, 12 or 5 times over the spontaneous mutation rate. After 6 h of exposure to vinyl chloride, the mutagenic response for TA 1530 strain was enhanced 7-, 4- or 5-fold when fortified postmitochondrial liver fractions from humans, rats or mice were added. The enzyme-mediated vinyl chloride mutagenicity was dependent on an NADPH generating system and the enzyme activity was localized in a liver microsomal fraction; 9,000 times g liver supernatant was three times more active than microsomes, while liver cytosol or alcohol dehydrogenase did not affect the mutagenicity. Phenobarbitone pretreatment of rats and mice increased the mutagenic response by up to 15-40 percent as compared to untreated controls. The relative mutagenic activities of VCM, taking the value from mouse liver as 100, for TA 1530 strain mediated by 9,000 times g tissue fractions were: rat liver, 80; mouse and rat kidney, 20 and 16; mouse and rat lung, less than 7; human liver (from four biopsy specimens) 170, 64, 70 and 46. Chloroacetaldehyde and chloroacetic acid, a urinary metabolite of VCM, showed toxic effects, while chloroethanol was weakly mutagenic for TA 1530 strain.

Acetaldehyde↗
PubMed1975

Junctions between sinusoidal endothelial cells in fetal rat liver.

During a freeze-fracture study of tight junctions in fetal rat liver (Montesano et al., '75) unusual patterns of intramembranous particles were observed in regions of contact between sinusoidal endothelial cells. These patterns were mainly represented by arrays of particles, often associated with linear elevations or crests in the membrane A-face; they may represent abortive forms of tight junctions.

Animals↗
PubMed1975

The modification of the renal carcinogenicity of dimethylnitrosamine by actinomycin D and a protein deficient diet.

The effect of a single treatment with 30 mg dimethylnitrosamine (DMN) and 6 mug actinomycin D (ACT), given at different time intervals (ACT application to DMN, 2 h before, simultaneously, 5, 9 or 48 h later), was tested in female Sprague-Dawley rats in relation to renal carcinogenesis; additionally, the animals were fed either a normal or a protein deficient diet. The ACT treatment did not significantly modify either the kidney tumour incidence or the survival time in the different groups fed a normal diet. Nevertheless, there are indications that additional ACT application may shorten the latency period for DMN induced renal neoplasms or, when administered 5 h later than DMN, a slightly decreased and delayed tumour induction can be assumed. In groups fed a protein deficient diet, a significantly higher percentage of kidney tumour bearing animals as well as a shortened latency period were found when compared with the DMN group on normal diet, but these differences were independent of the additional ACT treatment 9 h later than DMN and were due to the protein deprivation. Morphologically, the tumours were of epithelial and mesenchymal type with a clear preponderance of the former type. Biochemical and morphological aspects are discussed.

Adenoma↗
PubMed1975

In vivo assembly of tight junctions in fetal rat liver.

Examination of glutaraldehyde-fixed, freeze-fractured livers from 14-15-day rat fetuses provided the basis for the following observations. Membrane particles align in otherwise poorly particulated areas of the presumptive pericanalicular plasma membrane (A face), frequently forming a discontinuous "honey-comb" network joining small particle islands. Even at this early stage, contiguous B-fracture faces contain furrows, rather than rows of pits, distinguishing the linear particle aggregates on the A face as developing tight junctions rather than gap junctions. Short segments of these linear arrays merge with smooth ridges clearly identifiable as segments of discontinuous tight junctions. With the continuing confluence of particulate and smooth ridge segments, mature tight junctions become fully appreciable. We conclude that tight junctions form de novo by the alignment and fusion of separate particles into beaded ridges which, in turn, become confluent and are transformed into continuous smooth ones. At 21 days of fetal life, most of the images of assembly have disappeared, and the liver reveals well-formed bile canaliculi sealed by mature tight junctions.

Animals↗
PubMed1975

In vitro metabolism and microsome-mediated mutagenicity of dialkylnitrosamines in rat, hamster, and mouse tissues.

Rates of conversion of 14C-labeled dimethyl-and diethylnitrosamine by rat and hamster tissue slices to 14CO2 and/or into mutagenic reactants were measured using Salmonella typhimurium G-46 r TA 1530 and fortified tissue fractions in vitro. A correlation between the CO2 production from dimethyl- or diethylnitrosamine in liver or lung and the organ distribution of induced tumors in vivo was observed. As an exception, hamster lung, which is a major target organ in diethylnitrosamine carcinogenesis, did not convert this nitrosamine into metabolites mutagenic for S. typhimurium TA 1530 although the 14CO2 production in vitro was even higher than in hamster liver. The effect of pretreating rats, hamsters, and mice with phenobarbitone on the mutation frequency produced by dimethyl-or diethylnitrosamine in in vitro assays was determined. The relationship between the site of metabolic activation, mutagenicity, and carcinogenicity of the dialkylnitrosamines and the effect of enzyme inducers are discussed.

Animals↗