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Biomedical subjects

A Columbano

Publications and source records attributed to A Columbano.

At least 73 records · Page 4Linked to original sources
PubMed1987

Liver cell proliferation induced by the mitogen ethylene dibromide, unlike compensatory cell proliferation, does not achieve initiation of rat liver carcinogenesis by diethylnitrosamine.

The purpose of this investigation was to determine whether mitogen-induced cell proliferation is as effective as compensatory cell proliferation in achieving initiation of carcinogenesis in rat liver. Male Wistar rats were injected with a single non-necrogenic dose of the hepatocarcinogen diethylnitrosamine (DENA) during the peak of DNA synthesis following the administration of the hepatic mitogen ethylene dibromide (EDB) or a necrogenic dose of CCl4. After subjecting the animals to a promoting procedure, the rats were sacrificed and the initiated hepatocytes were monitored as gamma-glutamyltranspeptidase (gamma-GT) positive foci. The results indicate that while DENA administration during compensatory cell proliferation results in the formation of GT positive foci, no enzyme-altered foci were produced when the carcinogen was given during liver hyperplasia induced by EDB, despite the fact that at the time of carcinogen administration, the extent of cell proliferation, as monitored by thymidine incorporation into DNA, was the same in both the groups.

Animals↗
PubMed1987

Cell proliferation in rat kidney induced by 1,2-dibromoethane.

The effect of a single intragastric injection of 1,2-dibromoethane was investigated in kidneys of male Wistar rats. DNA synthesis as measured by the incorporation of tritiated thymidine was found to be approximately 5 times greater than that of controls 20-30 h after treatment. DNA synthesis was followed by a striking increase in the mitotic activity with a maximum at 30 h. The labeling and mitotic activities, after an initial increase, fell rapidly 48 h after treatment even though they were still higher than those of control animals. 1,2-Dibromoethane-induced cell proliferation is not a regenerative response because at the dose used in this study, no tubular necrosis was observed by histologic examination.

Animals↗
PubMed1987

Failure of mitogen-induced cell proliferation to achieve initiation of rat liver carcinogenesis.

Experiments were designed to determine whether mitogen-induced cell proliferation is as effective as regenerative cell proliferation in achieving initiation of liver carcinogenesis. To test this hypothesis male Wistar rats were injected with a single dose of diethylnitrosamine (DENA) or N-methyl-N-nitrosourea (MNU) during the peak of DNA synthesis following the administration of the liver mitogen, lead nitrate, after partial hepatectomy (PH) or a necrogenic dose of CCl4. The initiated hepatocytes were monitored as gamma-glutamyltransferase (GGT)-positive foci using a 2-week selection regimen consisting of 0.03% 2-acetylaminofluorene (2-AAF) coupled with a necrogenic dose of CCl4. The results indicate that unlike compensatory cell proliferation such as that induced by PH or CCl4, mitogen-induced cell proliferation did not result in any initiated hepatocytes despite the fact that in both types of models the extent of liver cell proliferation at the time of the administration of the carcinogen is similar.

Animals↗
PubMed1987

HMP-shunt and cholesterol metabolism in experimental models involving normal and preneoplastic liver growth.

Previous studies from our laboratories have shown a stimulation of HMP-shunt, cholesterol metabolism and DNA synthesis during cell proliferation. In order to understand the co-ordinated regulation of these pathways during cell growth, the above metabolic pathways were studied in: liver regeneration after partial hepatectomy, lead-induced liver hyperplasia, liver cell proliferation induced by insulin in streptozotocin-diabetic rats, liver cell proliferation in fasted rats after refeeding and, hepatocyte nodules induced by a selection procedure. The results indeed indicate that changes in HMP-shunt and cholesterol metabolism occur at a very early stage during the process of normal as well as preneoplastic cell growth. The coordinated regulation between cell growth and changes in these metabolic pathways needs further study.

Animals↗
PubMed1987

Induction of the placental form of glutathione S-transferase by lead nitrate administration in rat liver.

The administration of a single dose of lead nitrate to male Wistar rats caused an increase of a polypeptide in the liver cytosol that cross reacted with the anti-rat antibody of the placental form of glutathione S-transferase (GST-P). GST-P appeared when doses of lead that induced liver cell proliferation were given (5 and 10 micromoles/100 g of body weight). Recently, it has been shown that rat hepatic nodules also exhibited an increased content of the placental form of GST-P. The induction of GST-P by lead together with other biochemical effects exerted in the liver by this metal, suggests that some chemicals may induce in rat liver a biochemical pattern similar, in some aspects, to that exhibited by carcinogen-induced hepatocyte nodules.

Animals↗
PubMed1986

Lead nitrate induces certain biochemical properties characteristic of hepatocyte nodules.

Hepatocyte nodules in the rat exhibit a unique biochemical pattern which is characterized by a decrease in Phase I and an increase in Phase II components of the drug-metabolizing system. The present study was designed to determine whether this biochemical pattern is unique for rat hepatocyte nodules or is a property of the liver cell, but expressed only when the liver cell is perturbed. The results obtained indicate that lead nitrate (5 or 10 mumol/100 g body wt), an inducer of liver cell proliferation, caused a decrease in Phase I components such as microsomal cytochromes P-450 and in the activity of aminopyrine N-demethylase, while it caused an increase in Phase II components such as glutathione, and in the activities of glutathione-S-transferase and DT-diaphorase in rat liver. Of particular interest was the finding in liver cytosol of lead-treated rats of an increased content of a polypeptide which cross-reacts with the anti-rat placental form of glutathione-S-transferase. Recently, it has been shown that rat hepatocyte nodules exhibited an increased content of the placental form of glutathione-S-transferase. Thus, the results suggest that some chemicals, such as lead nitrate, can induce in rat liver a biochemical pattern similar in certain respects to that exhibited by hepatic nodules. These chemicals may be used as model compounds to understand the molecular mechanism(s) underlying the induction of new and unique biochemical machinery seen in hepatic nodules.

Animals↗
PubMed1985

Enhancement of cholesterol synthesis and pentose phosphate pathway activity in proliferating hepatocyte nodules.

The endogenous synthesis of cholesterol in hepatocyte nodules, induced in male Wistar rats, by a single dose of the hepatocarcinogen diethylnitrosamine followed by a selection procedure, was investigated and was compared with that in surrounding and control tissue. In addition, the activity of enzymes related to carbohydrate metabolism (glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, glucose-6-phosphatase and pyruvate kinase), was measured. Hepatocyte nodules showed a striking increase in their capacity for synthesizing cholesterol, in comparison to surrounding and control tissues, and an enhancement in the activity of the pentose phosphate pathway, as indicated by increased activity of glucose-6-phosphate dehydrogenase and of 6-phosphogluconate dehydrogenase, and a concomitant decrease of glucose-6-phosphatase. The stimulation of cholesterol synthesis and of the pentose phosphate pathway was associated with increased incorporation of labelled thymidine into DNA. These data indicate that, among other metabolic disturbances, enhancement of cholesterol synthesis and of the pentose phosphate pathway, is accompanied by an increased proliferative capacity of hepatocyte nodules.

Animals↗
PubMed1985

Occurrence of cell death (apoptosis) during the involution of liver hyperplasia.

A single intravenous injection of lead nitrate at a dose of 10 mumoles/100 gm of body weight caused liver enlargement associated with hepatic cell proliferation. In the present study the involution of liver hyperplasia which follows the withdrawal of lead was studied in male Wistar rats. Histologic examination of liver sections from rats killed during the regression of the liver did not show any sign of massive lytic cell necrosis; no variation in the levels of serum glutamate pyruvate transaminase could be observed during the same time period; however, light microscopic observation of sections from the involuting liver showed the presence of several apoptotic bodies; the occurrence of apoptotic bodies was also confirmed by ultrastructural examination. Their incidence was found to be markedly increased at 5 days after treatment, a time period when the liver is already regressing; very few apoptotic bodies were observed in control animals or in treated rats 2 days after lead injection, a time point when mitotic index reached its maximum, or at 15 days, when the liver had returned to control values. These findings suggest that removal of excess liver which follows the initial hyperplasia caused by lead is due to a controlled mode of cell death, namely, apoptosis.

Alanine Transaminase↗
PubMed1984

Stimulation of DNA synthesis after a single administration of cadmium nitrate.

The effect of a single intravenous (i.v.) injection of cadmium nitrate was investigated in livers of male Wistar rats. A significant increase in liver weight, accompanied by an elevation of total hepatic DNA content was observed. DNA synthesis as measured by the incorporation of [3H]thymidine, was found to be 6 times greater than the control, at 24 h after treatment, and remained elevated over a period of 72 h. This elevation in DNA synthesis was not a consequence of cell necrosis, since no increase of serum glutamate-pyruvate transaminase (SGPT) activity was observed.

Alanine Transaminase↗
PubMed1984

Liver hyperplasia and regression after lead nitrate administration.

The effect of a single intravenous injection of lead nitrate on liver, was investigated in male Wistar rats. Lead nitrate at 5 and 10 mumoles/100 g of body weight stimulated a 19-fold increase in the incorporation of 3H-thymidine into liver DNA and resulted in temporal changes in DNA synthesis, as determined by assays of specific activity. Thirty-six hours after lead nitrate administration, the incorporation of 3H-thymidine reached its maximum and returned to normal levels within 3 days. A significant increase in the number of cells entering mitosis at 36 hours indicated the capacity of lead to stimulate liver cell proliferation. Enlargement of the liver after lead treatment was also observed in both female Wistar rats as well in male Fischer rats. This stimulatory effect of lead on liver growth was reversible; during the involution of the liver, cell death morphologically similar to the one described as apoptosis was observed in histological sections of liver from animals sacrificed 4-7 days after lead treatment.

Animals↗
PubMed1984

Occurrence of cell death (apoptosis) in preneoplastic and neoplastic liver cells. A sequential study.

A sequential study was performed to investigate the occurrence of cell death in preneoplastic and neoplastic liver cells of F-344 rats. The animals were administered a single initiator dose of 1,2-dimethylhydrazine and were then subjected to a liver carcinogenesis promotion regimen, consisting of a diet containing 1% orotic acid. Cell death, morphologically similar to that described as apoptosis, was evident in foci of preneoplastic hepatocytes at 10 weeks after orotic acid feeding. An increased frequency of apoptotic bodies was observed in nodules, but not in the surrounding liver, 20 weeks after starting the dietary regimen, and in hepatocellular carcinomas that developed after 1 year of continuous promotion. Occurrence of this type of cell death was also observed in liver foci of rats subjected to two other promoting regimens, suggesting, thus, a possible relevance of apoptosis to the carcinogenic process in the liver.

Animals↗
PubMed1984

[The interposed jejunal loop after resection for gastric ulcer (endoscopic study)].

Authors refer about an endoscopic study concerning twenty patients who have been previously operated for gastric ulcer. In these patients it was performed a reconstruction of the alimentary canal by means of a gastro-duodenal interposition of an isoperistaltic jejunal loop. Authors show that this method has been proved valid to prevent duodeno pancreatic reflux in the residual gastric sac.

Adult↗
PubMed1983

Lead and liver cell proliferation. Effect of repeated administrations.

The effect of repeated treatments with lead on hepatic cell proliferation was investigated in male Wistar rats. The animals were given intravenous injections of lead nitrate once every 10 days for 30 and 80 days. At the end of the experimental regimen, enlargement of the liver, accompanied by an increase in hepatic DNA content, was observed. A significant enhancement in the incorporation of labeled thymidine into hepatic DNA was found in lead-treated rats at the time intervals mentioned above, when compared with controls. An increase in the number of liver cells involved in mitosis was also observed in lead-treated animals. Analysis of serum glutamic-pyruvic transaminase and histologic observations did not show any sign of cell death at the time points examined. These results indicate that liver cells exposed to repeated treatments with lead undergo proliferation. However, a progressive reduction in the capacity of hepatic cells to divide was found in rats given repeated administrations of the metal, when compared with the extent of cell proliferation induced by a single dose of lead nitrate.

Alanine Transaminase↗
PubMed1983

Liver cell proliferation induced by a single dose of lead nitrate.

Treatment of male Wistar rats with a single dose of lead nitrate caused a marked enlargement of the liver, which reached its maximum 3 days after the administration of the metal salt. This grossly anatomic effect was accompanied by biochemical changes such as an increase in total protein and DNA content, with a maximum at 3 and 4 days, respectively. A partial regression of liver weight and total DNA and protein content occurred 7 days after lead administration; a significant increase in DNA concentration was found after 1 week, while no variation in protein, when expressed as milligrams per gram liver, was observed in lead-treated rat liver. An increase in DNA synthesis, as monitored by the incorporation of labeled thymidine, was also observed. An enhancement in the specific radioactivity of DNA was evident at 24 hours and appeared maximal at 36 hours after the administration of lead nitrate. The ability of lead to stimulate liver cell proliferation was shown by a significant increase of cells entering mitosis, with a peak at 48 hours. This mitogenic stimulus occurred in parenchymal as well as in nonparenchymal cells, thus showing that this effect was not unique to a particular liver cell populations. No detectable cell necrosis, as monitored by histologic observation, was seen in the liver of lead-treated rats, thus indicating that the cellular proliferation induced by lead is not due to a regenerative response. Only a slight elevation in the levels of serum glutamate-pyruvate transaminase (GPT) was observed by biochemical analysis.

Alanine Transaminase↗
PubMed1981

Requirement of cell proliferation for the initiation of liver carcinogenesis as assayed by three different procedures.

Experiments were designed to determine the role of cell proliferation in the initiation of liver carcinogenesis induced by chemicals. To investigate this, two methylating carcinogens, N-methyl-N-nitrosourea and 1,2-dimethylhydrazine, were used as the initiating carcinogens. The initiated hepatocytes were monitored by selectively stimulating them to grow into focal islands of presumptive preneoplastic hepatocytes. The experimental approach in brief consisted of the following. Rats received a nonnecrogenic dose of the carcinogen; at a time period when the carcinogen could no longer be detected in the system, they were subjected to either partial or sham hepatectomy. The initiated cell thus formed were selectively stimulated to grow into foci of preneoplastic hepatocytes using three different selection regimens: (a) feeding a diet containing 0.02% 2-acetylaminofluorene plus one administration of carbon tetrachloride (2 ml/kg body weight) intragastrically; (b) feeding a diet containing 0.05% phenobarbital; and (c) feeding a choline-deficient diet. The foci were quantitated by staining them for the presence of gamma-glutamyltransferase. The results obtained indicate that irrespective of the type of selection procedure used foci of preneoplastic hepatocytes were seen only in rats that received the carcinogen coupled with a cell-proliferative stimulus such as partial hepatectomy. Very few or no foci were seen in rats that received the carcinogen plus sham hepatectomy. These results suggest that cell proliferation plays an important role in the initiation of liver carcinogenesis by chemicals.

Animals↗
PubMed1980

In vivo replication of hepatic deoxyribonucleic acid of rats treated with dimethylnitrosamine: presence of dimethylnitrosamine-induced O6-methylguanine, N7-methylguanine, and N3-methyladenine in the replicated hybrid deoxyribonucleic acid.

Experiments were designed to determine whether some chemical lesions such as O6-methylguanine, N7-methylguanine, and N3-methyladenine induced in rat liver DNA by the hepatocarcinogen dimethylnitrosamine permit replication in vivo. For this purpose, [14C]dimethylnitrosamine was administered to methylate the parental strand of liver DNA. Four hours later, a time period when the carcinogen cannot be detected in either the liver or the blood, rats were subjected to partial hepatectomy in order to induce DNA replication. During the S phase, 5-bromo-2-deoxyuridine was administered to render the newly made strands heavy. The rebanded, hybrid, hepatic DNA of density 1.714 g/cm3 and greater was pooled from the neutral cesium chloride gradient, dialyzed, and lyophilized. The hybrid DNA was then treated with S1 nuclease to digest any single-stranded regions. The results obtained indicated the presence of O6-methylguanine, N7-methylguanine, and N3-methyladenine in S1 nuclease resistant, hybrid DNA. The results are interpreted to indicate that these chemical lesions permitted in vivo DNA replication.

Adenine↗