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British Journal of Cancer May 1975
Topics: Dimethylnitrosamine; Enzyme Activation; Liver Neoplasms; Nitrosamines; Saccharomyces cerevisiae
PubMed: 1098686
DOI: 10.1038/bjc.1975.101 -
Biological & Pharmaceutical Bulletin Dec 2004Mycelia of the edible mushroom Lentinus edodes (shiitake) were cultivated in a solid medium, and two fractions were obtained by hot-water extraction (L.E.M.) and then... (Comparative Study)
Comparative Study
Mycelia of the edible mushroom Lentinus edodes (shiitake) were cultivated in a solid medium, and two fractions were obtained by hot-water extraction (L.E.M.) and then ethanol extraction followed by Sephadex LH-20 column chromatography (ESMe). The L.E.M. and ESMe were then examined for their hepatoprotective effect on dimethylnitrosamine-injured mice. Both fractions decreased the blood aspartate aminotransferase and alanine aminotransferase levels, partially inhibited the overaccumulation of collagen fibrils, and suppressed the overexpression of genes for alpha-smooth muscle actin and/or heat-shock protein 47 in the mice. Both fractions also inhibited the morphologic change and proliferation of isolated rat hepatic stellate cells (HSCs), which play a central role in liver fibrosis, in a dose-dependent manner and without cytotoxicity. The direct interaction between the extracts and HSCs appears to be important for the hepatoprotective activity. Polyphenols contained in both fractions are considered to be potential candidates for expressing the hepatoprotective effects. The finding of antifibrotic activity in extracts from an edible mushroom is expected to be helpful in the development of hepatoprotective agents with few side effects.
Topics: Animals; Cells, Cultured; Dimethylnitrosamine; Fungal Proteins; Liver; Male; Mice; Mice, Inbred BALB C; Polysaccharides; Rats; Rats, Sprague-Dawley; Shiitake Mushrooms
PubMed: 15577212
DOI: 10.1248/bpb.27.1957 -
Journal of Toxicology and Environmental... Jan 1978The relationship between oxidative metabolism and acute toxicity of dimethylnitrosamine (DMN) was examined in neonatal and adult rats to take advantage of developmental...
The relationship between oxidative metabolism and acute toxicity of dimethylnitrosamine (DMN) was examined in neonatal and adult rats to take advantage of developmental changes in activity of the metabolizing enzymes. The objective was to determine the extent to which CO2 production from DMN is correlated with toxicity. Neonatal rat liver and kidney demonstrated the ability to metabolize DMN. This ability progressed to a maximum activity in liver between the 5th and 21st d of age and in kidney between the 15th and 21st d of age. After weaning, the activity of DMN oxidation decreased with age in both tissues. Evidence is also presented to suggest that more than one enzyme may be responsible for the oxidation of DMN to CO2 and that the predominance of individual enzymes varies as the neonate develops. Estimates of LD50 values, used to quantitate the acute toxicity of DMN at various ages, suggest that the rat is most sensitive to DMN toxicity at 5 d of age; however, conversion of DMN to CO2, both in vitro and in vivo, was not well correlated with acute toxicity.
Topics: Age Factors; Animals; Carbon Dioxide; DNA; Dimethylnitrosamine; Female; In Vitro Techniques; Kidney; Kinetics; Lethal Dose 50; Liver; Male; Nitrosamines; Oxidation-Reduction; Pregnancy; Rats
PubMed: 633406
DOI: 10.1080/15287397809529653 -
Chemico-biological Interactions Aug 1984Unscheduled DNA synthesis (UDS), following exposure to dimethylnitrosamine (DMN), was potentiated in cultured hepatocytes isolated following treatment of rats for 14 or...
Unscheduled DNA synthesis (UDS), following exposure to dimethylnitrosamine (DMN), was potentiated in cultured hepatocytes isolated following treatment of rats for 14 or 28 days with 20% ethanol/5% sucrose solution. Ethanol treatment was associated with increased UDS, a concomitant increase in hepatic microsomal protein concentration and DMN N-demethylase activity. Increased aniline hydroxylase activity of hepatic microsomes from ethanol-treated rats preceded the measured increase in microsomal protein content or DMN metabolism. The increase in metabolism of DMN in vitro and potentiation of DMN-induced UDS associated with ethanol treatment may contribute to a synergistic effect of ethanol on DMN hepatotoxicity and carcinogenicity. In contrast, ethanol pretreatment did not increase the cytotoxicity of DMN as characterized by enzyme release.
Topics: Aminopyrine; Aniline Compounds; Animals; DNA Repair; Dealkylation; Dimethylnitrosamine; Drug Synergism; Ethanol; In Vitro Techniques; L-Lactate Dehydrogenase; Liver; Male; Microsomes, Liver; Mutagens; Rats; Rats, Inbred F344
PubMed: 6744470
DOI: 10.1016/0009-2797(84)90039-5 -
Biochemical Pharmacology 1978
Topics: Animals; Carbon Dioxide; Diet; Dimethylnitrosamine; Formaldehyde; Kinetics; Lethal Dose 50; Male; Nitrosamines; Rats; Thiamine Deficiency
PubMed: 568470
DOI: 10.1016/0006-2952(78)90558-0 -
JAMA Oct 1983Dimethylnitrosamine (DMNA), a carcinogen, was detected at levels up to 32 micrograms/L in dialysate from five of 16 dialysis units surveyed. Blood drawn from patients at...
Dimethylnitrosamine (DMNA), a carcinogen, was detected at levels up to 32 micrograms/L in dialysate from five of 16 dialysis units surveyed. Blood drawn from patients at one of these units in which DMNA was raised in the dialysate showed a significant increase in the amount of DMNA in the patient's blood when predialysis levels were compared with 15-minute intradialysis levels. The presence of a mixed-bed deionizer without an antecedent carbon filter appeared to be necessary for DMNA production. These data suggest that DMNA is generated in certain water purification systems and may then diffuse into the patient's blood. Guidelines for deionizer-treated water should be revised to include an activated carbon filter.
Topics: Adolescent; Adult; Dimethylnitrosamine; Female; Humans; Male; Mass Spectrometry; Renal Dialysis; Retrospective Studies; Solutions; Water
PubMed: 6620504
DOI: No ID Found -
Chemico-biological Interactions 1988N-nitrosodimethylamine N-demethylase activity, DNA alkylation, capacity for O6-methylguanine repair and cell proliferation were measured in livers of newborn and adult... (Comparative Study)
Comparative Study
N-nitrosodimethylamine N-demethylase activity, DNA alkylation, capacity for O6-methylguanine repair and cell proliferation were measured in livers of newborn and adult CFW mice after a single carcinogenic dose of DMNA. DNA alkylation was found in newborn and adult mouse livers but it was significantly higher in the newborn. 6- and 7-methyl substitutions of guanine were identified by HPLC analysis in newborn and in adult mouse livers. Metabolic 14C incorporation into adenine and guanine was observed only in liver DNA of newborns. O6-methylguanine levels were higher in newborn than adult mice after a single i.p. dose of [14C]DNMA. Liver DNA repair capacity measured as O6-meG-DNA methyltransferase was higher in adults than in newborns. De novo liver DNA synthesis was more inhibited by DMNA pretreatment in newborn than in adult mice. The relationship between these parameters and the greater neonatal liver tumor susceptibility is discussed.
Topics: Alkylation; Animals; Animals, Newborn; Biotransformation; Chromatography, High Pressure Liquid; Cytochrome P-450 CYP2E1; DNA; DNA Repair; Dimethylnitrosamine; Guanine; Liver; Methyltransferases; Mice; O(6)-Methylguanine-DNA Methyltransferase; Oxidoreductases, N-Demethylating
PubMed: 3214887
DOI: 10.1016/0009-2797(88)90020-8 -
Cancer Research Dec 1975Hepatic protein synthesis was investigated using a postmitochondrial supernatant system derived from the livers of rats that were given injections of a single dose of...
Hepatic protein synthesis was investigated using a postmitochondrial supernatant system derived from the livers of rats that were given injections of a single dose of dimethylnitrosamine (DMN), 30 mg/kg. The time course and extent of DMN-induced inhibition in vitro were identical to those reported for the incorporation of amino acids into liver proteins in vivo, maximum inhibition being about 70% at 5 hr. Addition of specific inhibitors of chain initiation (polyinosinic acid and aurin tricarboxylic acid) to the postmitochrondrial supernatant system from DMN-treated rats caused only a slight additional inhibition, indicating that DMN predominantly affects translation by a block of initiation. Treatment with cystamine prior to DMN administration completely abolished the depression of protein synthesis and reduced by more than 90% the methylation by [14C]DMN of purine bases in liver DNA. Pretreatment with pregnenolone-16alpha-carbonitrile stimulated protein synthesis in controls but had no preventive effect in DMN-treated rats and did not reduce the extent of DNA alkylation in vivo.
Topics: Alkylation; Animals; Aurintricarboxylic Acid; Cell-Free System; Cystamine; DNA; Depression, Chemical; Dimethylnitrosamine; Female; Guanine; In Vitro Techniques; Liver; Nitrosamines; Poly I; Polyribosomes; Pregnenolone; Protein Biosynthesis; Rats; Time Factors
PubMed: 1192427
DOI: No ID Found -
The Indian Journal of Medical Research Dec 1994Presence of volatile N-nitrosamines in beer and other alcoholic drinks are well documented in developed countries. Analysis of 120 beer samples of various brands/batches...
Presence of volatile N-nitrosamines in beer and other alcoholic drinks are well documented in developed countries. Analysis of 120 beer samples of various brands/batches showed positivity for N-nitrosodimethylamine (NDMA) in more than 100 samples. The overall mean of 3.6 ppb of NDMA is higher than those currently found in Western countries. Since N-nitrosamines are proven carcinogens in animals at several sites it is necessary to keep their levels of exposure to as low as possible.
Topics: Beer; Dimethylnitrosamine; India; Nitrosamines
PubMed: 7829171
DOI: No ID Found -
Biochemical Society Transactions 1975
Topics: Animals; Dimethylnitrosamine; Glucose-6-Phosphatase; Liver; Microsomes, Liver; Nitrosamines; Pyrazoles; Rats; Time Factors; Triazoles
PubMed: 165108
DOI: 10.1042/bst0030179