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Mutation Research Aug 1980The mutagenic effect of dimethylnitrosamine in Salmonella typhimurium TA100, in the presence of a rat-liver homogenate derived from animals treated with Aroclor 1254,...
The mutagenic effect of dimethylnitrosamine in Salmonella typhimurium TA100, in the presence of a rat-liver homogenate derived from animals treated with Aroclor 1254, was inhibited by substrates and inhibitors of monoamine oxidase. Substrates of diamine oxidase did not inhibit dimethylnitrosamine mutagenesis and, furthermore, monoamine oxidase inhibitors had no effect on mutagenesis by benzo[a]pyrene or aflatoxin B1. The results suggest that monoamine oxidase participates in the activation of dimethylnitrosamine to a mutagen.
Topics: Animals; Aroclors; Biotransformation; Chlorodiphenyl (54% Chlorine); Dimethylnitrosamine; Dose-Response Relationship, Drug; Male; Microsomes, Liver; Monoamine Oxidase; Monoamine Oxidase Inhibitors; Mutagens; Mutation; Rats; Salmonella typhimurium
PubMed: 7003365
DOI: 10.1016/0027-5107(80)90221-3 -
Annales de La Nutrition Et de... 1976Nitrosamines are an extremely carcinogenic class of compounds. The hasard, bound with the occurrence of this compounds in the food and the possibility to be formed in...
Nitrosamines are an extremely carcinogenic class of compounds. The hasard, bound with the occurrence of this compounds in the food and the possibility to be formed in vivo, during the digestion, justifies the current works. The authors quoting numerous works on different laboratory's animals, remind the toxicity. and carcinogenicity of this compounds. The metabolism is also discussed. The N-nitroso, compounds may be formed in food from the presence of the precursors (nitrite or nitrate, amines and amino-acides). The synthesis takes place during the technological processes, the storage and the house cooking. Today, the marginal effect dose is estimated as 10 mug/kg of daily food. The carcinogenicity has not been demonstrated in human, but is strongly suspected. The amount of N-nitroso compounds in human food is generally low. Many factors can influence the reaction; it is inversely related to the basicity of secondary amine and optimum pH is around pH 4. A lot of compounds such as sodium ascorbate inhibit the synthesis in food. A number of recent reports using reliable methodology have identified nitrosamines at the lower part per billion level. Dimethyl-nitrosamines occurs, very sporadically in a number of cooked meat samples. The nitrosopyrrolidine appears frequently in fried but not in uncooked products. The nitrosopiperidine seems to be bind with the presence of pepper in food. Finally the presence of nitrosamides (nitrososarcosine) and nitrosoaminoacides (nitrosoproline, nitrosohydroxy-proline) is being quested. The N-nitroso compounds may be synthetized in vivo during the digestion at the acide medium of the stomach or by bacterial action during the transit in the gut...
Topics: Amino Acids; Dimethylnitrosamine; Food Analysis; Humans; Neoplasms; Nitrites; Nitrosamines
PubMed: 1015737
DOI: No ID Found -
Journal of Forensic Sciences Oct 1980In an 8-h period, five members of two kindred families suddenly became ill with nausea, vomiting, and malaise. This was followed by acute liver disease, a generalized...
In an 8-h period, five members of two kindred families suddenly became ill with nausea, vomiting, and malaise. This was followed by acute liver disease, a generalized bleeding tendency, and a low platelet count. Two of the patients died four and five days after onset of illness. It was established that dimethylnitrosamine had been intentionally added to lemonade and milk that were consumed by the victims.
Topics: Adult; Child, Preschool; Dimethylnitrosamine; Disease Outbreaks; Female; Homicide; Humans; Infant; Liver; Male; Tissue Distribution
PubMed: 7430995
DOI: No ID Found -
Food and Cosmetics Toxicology Feb 1980
Topics: Beer; Dimethylnitrosamine
PubMed: 7372206
DOI: 10.1016/0015-6264(80)90006-1 -
Bulletin of Environmental Contamination... Jun 1976
Topics: Air; Dimethylnitrosamine; Industry; Maryland; Nitrosamines; West Virginia
PubMed: 938767
DOI: 10.1007/BF01685626 -
Chemico-biological Interactions 1979In vivo administration to rats of the mixed-function oxidase modifiers 3-methylcholanthrene (MC), pregnenolone-16 alpha-carbonitrile (PCN) or beta-naphthoflavnoe...
In vivo administration to rats of the mixed-function oxidase modifiers 3-methylcholanthrene (MC), pregnenolone-16 alpha-carbonitrile (PCN) or beta-naphthoflavnoe (beta-f) inhibits the hepatic microsome-catalyzed in vitro binding of dimethylnitrosamine (DMN) to DNA. This parallels their effect on DMN-demethylase I, regarded to be the sole activating step in DMN carcinogenesis and fails to account for the previously observed anomaly that MC and PCN inhibit, while beta-NF enhances, the hepatocarcinogenic activity of DMN. The in vitro binding of DMN is clearly dependent on microsomes and NADPH, and is strongly enhanced by soluble cytoplasmic proteins; the presence of the latter has no effect. however, on the relative response to pretreatment by the modifiers. In mice beta-NF enhances and PCN inhibits DMN-demethylase I; beta-NF has no effect on either the cytochrome P-450 level or on the LD50, while PCN strongly increases the cytochrome P-450 level but without influencing the LD50. Neither of the two modifiers has any effect in mice on the host-mediated mutagenicity of DMN in a dose-response study, except for the highest dose of DMN (200 mg/kg) where PCN pretreatment significantly enhanced mutagenicity. To account for the anomalous observations, other potential pathways of DMN metabolism have been explored. Whole rat liver nuclei or isolated nuclear membrane fractions contain no DMN-demethylase or diethylnitrosamine-deethylase activity. In a microsomal mixed-function amine-oxidase assay system neither purified enzyme preparations nor whole microsomes catalyze NADPH oxidation in the presence of DMN as substrate. In addition, the purified enzyme does not catalyze formaldehyde production in the DMN-demethylase assay system. Benzylamine, a typical inhibitor of mitochondrial monoamine oxidase (MAO), is a potent inhibitor of DMN-demethylase activity, but microsomes are devoid of MAO activity. Furthermore, purified MAO has no DMN-demethylase activity. The differential effect of modifiers on the carcinogenicity of DMN probably involves pathways other than DMN metabolism.
Topics: Biotransformation; Cell Nucleus; DNA; Dimethylnitrosamine; Flavonoids; Microsomes, Liver; Mutagens; Oxidoreductases Acting on CH-NH Group Donors; Oxidoreductases, N-Demethylating; Pregnenolone Carbonitrile
PubMed: 498363
DOI: 10.1016/0009-2797(79)90118-2 -
Ecotoxicology and Environmental Safety Dec 1982In order to evaluate the contribution of volatile nitrosamines from tobacco smoke to indoor air pollution, N-nitroso-dimethylamine (NDMA) and N-nitroso-diethylamine...
In order to evaluate the contribution of volatile nitrosamines from tobacco smoke to indoor air pollution, N-nitroso-dimethylamine (NDMA) and N-nitroso-diethylamine (NDEA) were measured in indoor air under artificial and natural conditions. In controlled experiments under extreme conditions, we found that tobacco smoke-related NDMA levels above 0.07 ng/liter were associated with a highly irritating atmosphere which was scarcely tolerable to those present. In smoke-filled rooms under natural conditions NDMA levels ranged from 0.02 to 0.05 ng/liter except a minimum value of less than 0.01 ng/liter in a restaurant and a maximum of 0.07 ng/liter in a dancing bar. These NDMA levels are thus below comparable values reported by others. The NDMA/NDEA ratios found in air samples taken from some rooms under conditions of everyday life are quite different from those found in sidestream smoke of cigarettes. Irritation was not reported under natural conditions. From the results it is concluded that NDMA levels, measured under real life conditions, are usually not caused by tobacco smoke alone. Evidence for other sources of volatile nitrosamines is discussed.
Topics: Air; Air Pollutants; Dimethylnitrosamine; Humans; Tobacco Smoke Pollution
PubMed: 7169041
DOI: 10.1016/0147-6513(82)90031-8 -
Food and Chemical Toxicology : An... Apr 1995Human skin penetration of N-dimethylnitrosamine (DMN) from three vehicles has been determined in vitro. When applied as an infinite dose in isopropyl myristate (IPM, 1... (Comparative Study)
Comparative Study
Human skin penetration of N-dimethylnitrosamine (DMN) from three vehicles has been determined in vitro. When applied as an infinite dose in isopropyl myristate (IPM, 1 microgram/microliter) the average total absorption over 48 hr was 2.6 +/- 1.2% of the applied dose (all data presented are expressed as means +/- standard errors). When applied as a finite dose in a representative oil-in-water emulsion vehicle the average total absorption over 48 hr was 4.0 +/- 0.3% of the applied dose. When applied as a finite dose in a representative shampoo vehicle for 10 min followed by rinsing (i.e. to represent in-use exposure conditions) the average total absorption over 48 hr was 1.1 +/- 0.1% of the applied dose. Approximately 72% of the DMN in the applied shampoo vehicle was removed by rinsing. There was considerable evaporative loss of DMN from the IPM and oil-in-water emulsion vehicles, such that absorption was complete within 3 hr of application. The overall data indicate that DMN can penetrate the skin rapidly but that in practice the amount actually available for penetration is significantly reduced by high permeant volatility. In contrast, application of N-nitrosodiethanolamine (NDELA) at a concentration of 1 microgram/microliter as an infinite dose generated an average total absorption over 48 hr of 23.6 +/- 6.4%, representing a total flux of 103.9 +/- 28.4 micrograms/cm2. In the case of NDELA, no evaporative loss was evident.
Topics: Carbon Isotopes; Cosmetics; Dimethylnitrosamine; Emulsions; Female; Hair Preparations; Humans; In Vitro Techniques; Isotope Labeling; Myristates; Oils; Skin Absorption; Solubility; Volatilization; Water
PubMed: 7737604
DOI: 10.1016/0278-6915(94)00146-f -
Advances in Experimental Medicine and... 1981
Topics: Animals; Carbon Radioisotopes; DNA; Dimethylnitrosamine; Kinetics; Liver; Proteins; RNA; Rats; Rats, Inbred Strains
PubMed: 6178269
DOI: No ID Found -
Mutation Research Oct 1984Chemically-induced DNA repair was measured as unscheduled DNA synthesis (UDS) in selected tissues isolated from rats following in vivo exposure to inhaled...
Chemically-induced DNA repair was measured as unscheduled DNA synthesis (UDS) in selected tissues isolated from rats following in vivo exposure to inhaled dimethylnitrosamine (DMN). UDS was evaluated in epithelial cells from rat nasal turbinates and trachea, in hepatocytes and in pachytene spermatocytes from the same treated animal. At nominal concentrations of 500 and 1000 ppm of DMN in air, chemically-induced DNA repair was observed in the epithelial cells of the upper respiratory system. DMN also entered the circulation, as evidenced by a strong DNA-repair response in hepatocytes. No DNA repair was observed in pachytene spermatocytes indicating either that DMN or its active metabolites did not reach the testes in sufficient concentration to induce DNA repair or that the testes lacked the capability to metabolically activate the compound. These results illustrate the potential of this approach to assess the organ-specific genotoxicity of environmental chemicals.
Topics: Animals; DNA; DNA Repair; Dimethylnitrosamine; Gases; Male; Rats; Tissue Distribution
PubMed: 6493268
DOI: 10.1016/0165-7992(84)90023-x