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Biomedical subjects

R Montesano

Publications and source records attributed to R Montesano.

At least 253 records · Page 14Linked to original sources
PubMed1979

Persistence of methylated bases in ribonucleic acid of syrian golden hamster liver after administration of dimethylnitrosamine.

1. Syrian golden hamster liver ribosomal RNA was isolated up to 96 h after administration of [14C]dimethylnitrosamine at 25 mg/kg or 2.5 mg/kg body weight. 2. The chemical alkyation products, 7-methylguanine, 3-methylcytosine, O6-methylguanosine and 1-methyladenosine, were measured after acidic or enzymic hydrolysis of the RNA to bases or mononucleosides followed by ion-exchange chromatography. 3. Between 7 and 96 h, the relative amounts of alkylation products did not change with time even though the absolute amounts fell by approx. 80% and 51% after the high and low doses respectively. 4. The results suggest that base specific excision repair does not exist for RNA alkylation products in this experimental system.

Alkylation↗
PubMed1979

Inhomogeneous distribution of filipin-sterol complexes in the ciliary membrane of rat tracheal epithelium.

Pieces of rat trachea fixed in a glutaraldehyde solution containing 300 muM filipin, a sterol-specific polyene antibiotic (Elias et al., '78), were freeze-fractured in order to study the distribution of cholesterol within the ciliary membrane. Filipin-sterol complexes, recognizable as 25-30-nm protrusions on fracture faces, appeared densely and uniformly distributed over most of the ciliary membrane, but were absent from the region of the ciliary necklace. It is possible, therefore, that the ciliary necklace represents a cholesterol-poor area of membrane.

Animals↗
PubMed1979

Absence of filipin-sterol complexes from large coated pits on the surface of culture cells.

Monolayer cultures of normal or transformed fibroblasts and of liver cells fixed in a glutaraldehyde solution containing 300 microM filipin, a sterol-specific polyene antibiotic, were freeze-fractured to study the distribution of cholesterol within their plasma membranes. Filipin-sterol complexes, recognizable as 25- to 30-nm protuberances scattered in the fracture face of plasma membrane, were absent from invaginations corresponding to large, bristle-coated pits (and possibly also from small, flask-shaped invaginations). These results suggest that invaginating regions on the cell surface are specialized plasma membrane domains with a lower cholesterol content than the surrounding membrane. The localized change in membrane fluidity due to the low cholesterol concentration could play a role in endocytosis.

Animals↗
PubMed1979

gamma-Glutamyl transpeptidase and malignant transformation of cultured liver cells.

The relationship between gamma-glutamyl transpeptidase (GGT)and malignant cell transformation was analyzed in malignant and nonmalignant culture epithelial cell lines derived from rat livers and fibroblastic cell types derived from hamsters and mice. GGT activity was prominent (25 to 90% of cells) in 3 of 5 malignant epithelial liver cell lines. None of the 9 fibroblastic or 4 nonmalignant epithelial cell lines exhibited GGT activity. Our results suggest that by use of GGT activity we can detect in cultured liver cells a significant fraction of the spontaneously or chemically induced malignant cells. Thus, in conjunction with other markers, this marker may help in identifying tumorigenic cells in liver epithelial cultures.

Animals↗
PubMed1979

Increased excision of O6-methylguanine from rat liver DNA after chronic administration of dimethylnitrosamine.

Male BDIV rats were given dimethylnitrosamine (2 mg/kg daily) by stomach tube on weekdays for a total of 9 weeks, the final dose being of 14C-labeled material. Control rats received only the labeled dimethylnitrosamine. Liver DNA was isolated at various times later (from 2 to 12 hr), and normal and alkylated purines were determined after hydrolysis in mild acid by chromatography on Sephadex G-10. The levels (measured as dpm/micronmol of parent base) of 7-methylguanine in the DNA of the pretreated rats were the same as or slightly higher than those of the control animals, and the persistence of this product was similar in both groups. This was also true for 3-methyladenine. In contrast, the initial amount of O6-methylguanine in the liver DNA of the pretreated rats was one-third of the amount found in the control rats, and the rate of loss of this product from DNA was higher in the pretreated animals. These differences were reflected in the alkylation product ratios: the 3-methyladenine:7-methylguanine ratios were closely similar in the two groups of animals at all times, whereas the O6-methylguanine:7-methylguanine ratio was initially 3 times higher in the control animals and fell more slowly. DNA synthesis (as measured by the incorporation of [3H]thymidine) was higher in the liver, kidney, and lung of rats receiving dimethylnitrosamine pretreatment. These findings are discussed with respect to the hepatocarcinogenicity of chronically administered dimethylnitrosamine.

Animals↗
PubMed1978

Fenestrations in endothelium of rat liver sinusoids revisited by freeze-fracture.

The freeze-fracture appearance of fenestrations of sinusoidal endothelial cells has been reassessed in perfusion-fixed rat liver. Fenestrations, limited to the attenuated portions of the endothelial cell cytoplasm are usually round or oval in shape, with diameters ranging from 40-600 nm. Within a given fenestrated region, they are disposed in clusters forming sieve plates. In addition, the presence of wide, irregularly shape openings suggest that adjacent fenestrations may coalesce and result in the larger openings. Our data thus confirm the existence of both small and large fenestrae in the endothelial wall, in contradistinction to previous studies showing only regular, medium sized (100 nm) openings.

Animals↗
PubMed1978

Evaluation of the carcinogenicity of chemicals: a review of the Monograph Program of the International Agency for Research on Cancer (1971 to 1977).

In 1971 the International Agency for Research on Cancer initiated a program on the evaluation of the carcinogenic risk of chemicals to humans, which concentrated on the production of monographs on individual chemicals. A review of this ongoing program is presented here as a contribution to the discussion of primary prevention of cancer. A total of 368 chemicals were evaluated in the first 16 volumes of the International Agency for Research on Cancer monographs. For 26 chemicals (or industrial processes), a positive association between exposure and the occurrence of cancer in humans was observed. For 221 chemicals, some evidence of carcinogenicity was found in at least one species of experimental animals. However, no evaluation of the carcinogenic risk of these chemicals to humans was made, either because no epidemiological studies or case reports were available or because the results of available human studies were inconclusive. For the remaining 121 chemicals, the available data were inadequate for an evaluation of the presence or absence of a carcinogenic effect in experimental animals or humans. The criteria on which the carcinogenicity of chemicals to humans and/or experimental animals was assessed, from the initiation of this program in 1971 until 1977, have recently been revised and are briefly discussed.

Animals↗
PubMed1977

Accumulation of O6-methylguanine in non-target-tissue deoxyribonucleic acid during chronic administration of dimethylnitrosamine.

1. BD-IV rats were given labelled dimethylnitrosamine (2 mg/kg) by stomach tube on weekdays (Monday to Friday) for up to 24 weeks. The rats killed after 2, 4, 8, 16 and 24 weeks of treatment (72 h after the final dimethylnitrosamine gavage) and DNA was isolated from the pooled livers, kidneys and lungs. Purine bases were released from the DNA by mild acid hydrolysis and separated by Sephadex G-10 chromatography. 2. Throughout the experiment, the content of 7-methylguanine in liver DNA was approx. 16 times that in kidney and lung. The amount of this product increased in the DNA of all three tissues up to 16 weeks, but by 24 weeks had decreased by 20% in the liver and 46% in the other tissues. 3. O6-Methylguanine was not detected in liver DNA, but was easily measured in kidney and lung DNA after 4 weeks of dimethylnitrosamine administration. The amount of O6-methylguanine in kidney and lung DNA increased relative to that of 7-methylguanine, and by 24 weeks was 60% of the 7-methylguanine content in both tissues. 4. Incorporation of radioactive C1 breakdown products of dimethylnitrosamine into normal purines in DNA increased continuously in all three tissues. 5. The results are discussed with respect to the specific hepatocarcinogenic effect of chronic administration of dimethylnitrosamine and the possible contribution of increased DNA repair and DNA synthesis.

Adenine↗
PubMed1977

Alkylated purines in the DNA of various rat tissues after administration of 1,2-dimethylhydrazine.

[1,2-3H] Dimethylhydrazine (1,2-DMH) (300 mg/kg; 4 mCi/kg) was injected s.c. to BD-VI rats and the degree of DNA alkylation was measured in various tissues 3 h after the administration. The O6-methylguanine/7-methylguanine ratio was approx. 4 times higher in the colon's DNA (0.0565), the principal target organ of this carcinogen, than in the liver's DNA (0.0136). These findings are briefly discussed in relation to the organ specificity of this carcinogen.

Animals↗
PubMed1977

Effect of split doses of N-methyl-N-nitrosourea on DNA repair synthesis in cultured mammalian cells.

DNA repair was measured in human fibroblasts, mouse C3H 10 T 1/2 fibroblsts and rat hepatocytes by the non-semi-conservative incorporation of [3H]-TdR during DNA repair synthesis using liquid scintillation techniques. Confluent monolayers of these cells grown on cover slips were exposed to split doses (125 or 250 microgram/ml) of the mutagenic and carcinogenic alkylating agent MNU and DNA repair synthesis compared with that produced by a single dose (500 microgram/ml). No significant difference in DNA repair capacity was detected in the three cell lines treated with a single dose or split doses of MNU.

Cells, Cultured↗
PubMed1977

Test for malignant transformation of rat liver cells in culture: cytology, growth in soft agar, and production of plasminogen activator.

Three parameters were evaluated as diagnostic of the malignant potential of cultured rat liver epithelial cells: cytology, growth in soft agar, and production of extracellular plasminogen activator. A total of 22 tumorigenic and nontumorigenic cultures from 15 cell lines were sent coded from their originators to two different laboratories for the evaluation of these three parameters. Cytologic diagnosis and growth in soft agar were reliable means of determining the malignant potential of the cultured cells. However, the production of extracellular plasminogen activator showed little correlation with tumorigenicity. Of cytologic properties evaluated, the two that correlated best with malignant potential were increased cytoplasmic basophilia and and increased nuclear:cytoplasmic ratio.

Agar↗
PubMed1977

Legislation concerning chemical carcinogens in several industrialized countries.

A survey was carried out on legislation in 14 industrialized countries relating to the prevention of occupational cancers. Two types of legislation were considered in particular: that dealing specifically with chemical carcinogens in the working environment, and that relating to compensation for occupational cancers. The survey revealed that legislation prohibiting the manufacture of chemicals known to be carcinogenic in humans or known to represent a possible cancer hazard to humans exists only in a limited number of the 14 countries considered and does not cover the same chemicals in each country. Legislation concerning monetary compensation is more common in these countreis than is legislation providing for primary prevention. There are two fundamental deficiencies in even the more comprehensive legislation. First, some chemicals for which carcinogenicity in humans has been proved are still produced in large quantities and are not covered by legislation. Second, the criteria used to determine which chemicals may be hazardous to humans when only experimental evidence of carcinogenicity exists are overexclusive, while the allowed concentrations of some of the chemicals recognized as possibly hazardous to humans appear to be very high.

Australia↗
PubMed1977

Microsome-mediated mutagenesis in V79 Chinese hamster cells by various nitrosamines.

A microsome-mediated mutagenesis system has been established with the V79 Chinese hamster cell line. The cells, grown in monolayer, were treated with various nitrosamines in the presence of a postmitochondrial fraction ((S15) from rat liver and a reduced nicotinamide adenine dinucleotide-generating system for 1 hr, washed and incubated for 2 to 3 hr in fresh culture medium, and then plated for toxicity and mutagenicity assays. Mutation was determined by resistance to 20mug 8-azaguanine per ml. In this assay system, the S15 fraction and cofactors by themselves were not toxic to the cells; dose-related mutagenicity and cytotoxicity were induced by N-nitrosodimethylamine (DMN) only in the presence of the S15 fraction and cofactors. Pretreatment of rats with phenobarbitone led to an approximately 2-fold increase in the mutation rate over that with tissues from untreated rats with concentrations of DMN from 10 to 50 mM, while aminoacetonitrile pretreatment reduced the mutagenic effect. Methylcholanthrene pretreatment resulted in an increase in the mutation frequency with a higher concentration of DMN (50mM). Various other nitrosamines were also assayed in the presence or absence of the S15 fraction from phenobarbitone-pretreated rats and a reduced nicotinamide adenine dinucleotide phosphate-generating system. With the exception of N-nitrosomethylphenylamine, the carcinogenic nitrosamines (DMN, N-nitrosodiethylamine, N-nitrosodi-n-propylamine, N-nitrosodi-n-butylamine, N-nitrosodi-n-pentylamine, N-nitrosomethyl-n-propylamine, N-nitrosomorpholine, N-nitrosopyrrolidine, N-nitroso-N'-methylpiperazine, and N-nitrosomethylphenylamine) were mutagenic to the V79 Chinese hamster cells in the presence of the S15 fraction and cofactors. Neither N-nitrosodiphenylamine nor N-nitrosomethyl-tert-butylamine had a mutagenic effect. These findings show that chemical carcinogens can be tested for mutagenicity in cultured mammalian cells in the presence of a metabolic activation system. The results are discussed in relation to the carcinogenicity and mutagenicity of these compounds in other test systems.

Acetonitriles↗
PubMed1976

Methylated purines in the deoxyribonucleic acid of various Syrian-golden-hamster tissues after administration of a hepatocarcinogenic dose of dimethylnitrosamine.

1. DNA was extracted from livers, kidneys and lungs of Syrian golden hamsters at various times (up to 96h) after injection of a hepatocarcinogenic dose of [14C]dimethylnitrosamine. Purine bases were released from the DNA by mild acid hydrolysis and separated by Sephadex G-10 chromatography. 2. At 7h after dimethylnitrosamine administration liver DNA was alkylated to the greatest extent, followed by that of lung and kidney, the values for which were 8 and 3% respectively of those for liver. 3. The O6-methylguanine/7-methylguanine ratios were initially the same in all three organs and in the liver DNA of rats under similar conditions of dose. 4. O6-Methylguanine was the most persistent alkylated purine in all three hamster tissues. There was evidence for excision of 7-methyl-guanine, the highest activity for this being present in the liver. 5. Detectable amounts of the minor products 3-methyladenine, 1-methyladenine, 3-methylguanine and 7-methyladenine were present in most hamster tissues, and their individual rates of loss from liver DNA were determined. 6. Ring-labelling of the normal purines in DNA was highest in the liver, followed closely by the lung (80% of that in liver) whereas the kidney had very low incorporation (3% of that in liver). 7. The results are discussed with respect to the hepatotoxicity of dimethylnitrosamine, the miscoding potential of the various alkylation products and the induction of liver tumours in hamsters.

Adenine↗