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PubMedDate not supplied

Ultrastructure of gastric epithelium after exposure to mild environmental agents (sodium nitrate, saprol).

Environmental chemical agents usually affect the human organism in combination rather than alone. The objective of this study was to determine the effect on the gastric mucosa of the herbicide Saprol alone or in combination with the nitroso compound sodium nitrate. We examined the cells of the gastric endocrine system by electronmicroscopy, and recorded the ultrastructural nuclear and cytoplasmic changes. The herbicide Saprol did not significantly change the ultrastructure of the gastric epithelial cells. Marked changes were noted in nuclei, mitochondria, and secretory granules of the gastric endocrine cells after exposure to both Saprol and sodium nitrate. These changes were significantly more severe after the combined exposure than after sodium nitrate exposure alone. The most affected were the vasointestinal polypeptide-producing D1 cells.

Animals↗
PubMed1978

[Postnatal and transplacental carcinogenic effects of methyl methanesulphonate (MMS) and ethyl methanesulphonate (EMS) in hooded rats (author's transl)].

In the last years numerous investigations of the preferentially neurotropic carcinogenic action of different indirectly alkylating N-nitroso-compounds have been reported. Contrary to these the nuber of experiments, in which the effect of directly alkylating methyl methanesulphonate (MMS) and ethyl methanesulphonate (EMS) was studied is relatively small. Therefore, in own investigations on 4 groups of hooded rats of the inbred strain E the postnatal and prenatal effects of MMS and EMS were studied.

Age Factors↗
PubMed1990

[The role of nitrites in carcinogenesis].

Data from literature as well as the results of the author's investigations on the genotoxic and carcinogenic effects of sodium nitrite (SN) are presented. Carcinogenicity of SN detected in animal experiments proved to be connected with the formation of nitroso compounds from endogenous nitrosable precursors. Sodium nitrite possessed the transforming and promoting effects in the cell cultures as well as the mutagenic effects in the bacterial systems where predominant effect of SN as compared with N-nitrosodimethylamine (NDMA) was registered. The prolonged pretreatment with SN amplified the liver DNA damage in rats in case of NDMA endogenous synthesis.

Animals↗
PubMed1990

The effect of Chinese tea on occurrence of esophageal tumor induced by N-nitrosomethylbenzylamine in rats.

Five groups of rats (40 rats per group) were given five different varieties of Chinese tea (1 g/50 ml) and another two groups of rats (a positive control and a negative control) were given tap water as drinking water. Except for the negative control group, all the animals were intubated with N-nitrosomethylbenzylamine (NMBzA, 5 mg/kg body wt/week). Half of the animals in each group were sacrificed after 6 weeks and the remaining animals at the end of 12 weeks. The incidences of esophageal mucosa lesions (16-59%) at the end of 6 weeks were significantly lower in the tea-treated rats than in the positive control group (100%). The incidences of esophageal tumor at the end of 12 weeks (42-67%) were also significantly lower in the tea-treated groups than in the positive control group (90%). The same phenomenon was found with respect to the size and number of tumors in each tumor-bearing animal. The relative anticarcinogenic effects of the five varieties of Chinese tea were different. The Fujian oolong tea and jasmine tea exhibited the strongest effects. The results suggest that Chinese tea can effectively inhibit the carcinogenesis caused by an N-nitroso compound.

Animals↗
PubMed1975

Disappearance of nitrite from the rat stomach: contribution of emptying and other factors.

To help understand how intragastric nitrosation forms N-nitroso compounds, nitriet disappearance from the rat stomach was measured after food containing nitrite was given. In preliminary experiments, nitrite disappearance from buffered aqueous solutions became more rapid as the pH was lowered from 5 to 1 and, at a given pH, was more rapid in a slurry of commercial rat food. The disappearance of nitrite from buffer was little affected by the addition of pepsin, mucin, albumin, or rat gastric contents. When starved rats were given 5 g food with 1.82 mg nANO3/g, nitrate was not reduced to nitrite in the stomach. Five g food containing 154 mug NaNO2/g was administered similarly, and the total stomach (T) and glandular and nonglandular parts (G and NG) were analyzed after 1.5 hours. Weight and nitrite concentration of the stomach contents dropped linearly and the amount of nitrite dropped exponentially (with a half-life of 1.4 hr). Mean nitrite concentration in G was less than half that in NG. From similar experiments with phenol red, emptying accounted for 60% of nitrite loss from T. In G, nitrite concentration was reduced about 3 times due to dilution and 3 times due to other causes. Conditions in G, e.g., nitrite concentration, pH, and empyting time, were discussed in relation to carcinogenesis experiments with nitrite plus amines and amides.

Albumins↗
PubMedDate not supplied

Interaction of aromatic nitro compounds with reduced hepatic microsomal cytochrome P-450.

Aromatic nitro compounds interact with sodium dithionite-reduced microsomes to generate difference spectra characterized by a maximum at 400 nm and minima at 440 and 528 nm. Spectral binding constants of approximately 1 mM were calculated for ferrohemochromes in which nitrobenzene, p-nitrobenzoate, 2-nitrofluorene, and 2-nitronaphthalene served as ligands. Nitro binding affinity was increased approximately 3-fold by pretreatment of animals with phenobarbital (KS congruent to 0.3 mM). The interaction of nitro compounds with reduced microsomes from 3-methylcholanthrene-pretreated animals, however, failed to give discernable difference spectra. There is apparent mutual inhibition of binding of carbon monoxide, metyrapone, and nitro compounds with reduced cytochrome P-450, since addition of metyrapone or carbon monoxide to reference and sample cuvettes does not alter qualitative aspects of the nitro binding spectra, but only its magnitude. From the relative KS values, it is concluded that metyrapone and carbon monoxide interact with reduced cytochrome P-450 more tenaciously than nitro compounds.

Aerobiosis↗
PubMed1990

High level, regulated expression of the chimeric P-enolpyruvate carboxykinase (GTP)-bacterial O6-alkylguanine-DNA alkyltransferase (ada) gene in transgenic mice.

Transgenic animals expressing genes capable of repairing DNA may be a valuable tool to study the effect of DNA-damaging agents on tissue-specific carcinogenesis. For this reason, we constructed a chimeric gene consisting of the promoter-regulatory region of the phosphoenolpyruvate carboxykinase (GTP) (EC 4.1.1.32) (PEPCK) gene linked to the Escherichia coli ada gene coding for O6-alkylguanine-DNA alkyltransferase and the polyadenylate region from the bovine growth hormone gene. The PEPCK promoter results in gene expression in liver and kidney and is induced by hormones, and its transcription is regulated by diet. The chimeric PEPCK ada gene was injected into the male pronucleus of fertilized eggs to produce transgenic mice. Six of 65 developing mice contained 5-10 copies of the intact trans gene per genome. Two founders transmitted the trans gene in a heterozygous manner, whereas 3 transmitted as germ line mosaics and 1 did not transmit to F1 offspring. All F1 offspring carrying the PEPCK ada trans gene expressed ada mRNA in liver and kidney and produced a functional alkyltransferase with a protein molecular weight of 39,000 originating from the bacterial gene. Total alkyltransferase activity was increased in the liver of F1 offspring from all founder mice, but offspring of only one founder had elevated renal alkyltransferase levels. A diet high in protein markedly increased ada mRNA and alkyltransferase activity within 1 week in both liver and kidney, whereas a high carbohydrate diet for 1 week markedly reduced expression of PEPCK ada and alkyltransferase levels. Nontransgenic animals were unaffected by these dietary manipulations. During induction with a high protein diet, hepatic alkyltransferase in transgenic mice was 16.6 +/- 1.5 units/micrograms DNA (mean +/- SE) compared to 5.3 +/- 0.6 units/micrograms DNA in control animals. This level of alkyltransferase is higher than that in any mammalian tissue noted previously except human liver. Transgenic animals expressing high levels of alkyltransferase should help define the role of DNA repair in protection from carcinogenesis induced by N-nitroso compounds.

Animals↗
PubMedDate not supplied

[Experimental model for the risk from multiple exposures to antiparasitic agents and residues from the food preservation process].

The human environmental hazard in the last ten years is the most important problem for public health and prevention. Particularly, in agriculture, the continuous use of increased quantities of pesticides and nitroso compounds, such as fertilizers, is involved. The evaluation of exposure risk is complex because of A: --a1) the numerous categories of chemical substances used as pesticides. --a2) the different catabolic pathways that are followed by organisms for detoxification. B: the different categories of exposed people such as: --b1) industrial workers who are exposed to a single compound, in time; --b2) agricultural workers whose exposure is multiple, prolonged over time, and often, even at high doses; --b3) general population whose exposure is from residues from the food chain. C: different kinds of exposure: --c1) accidental, acute and massive, the most studied; --c2) chronic exposure, the most difficult to quantity and of which we do not have any chemical features available, nor do we have parameters or sensitive or specific exposure indexes. The complexity of exposure and the difficulty to derive adequate indexes both in rural environments and in the general population, explains why there are no existing regulation parameters regarding exposure of agricultural workers where as they exist for industrial workers (MAC and TLV). When it is not possible to evaluate the quantity of substances that are used and absorbed during the work shift, it is necessary to revert to effect index measurements. On one hand these refer to the chemical nature of the substances employed and to the knowledge regarding the catabolism that, from the compound, brings about metabolic inactivation, and on the other hand refers to metabolic modification which is easily measured with blood tests and urinalysis. For example urinary metabolites of substances assumed through various ways (DichloroDiphenyl Acetic Acid-DDA-) and DDT or modifications of enzymes activity e.g. cholinesterasis following the manipulation of phosphoric compounds or alkaline phosphatasis from dithiocarbamates. Our experimental testing found that the systematic reduction of enzymes activity in serum of workers exposed to dithiocarbamates cannot be explained exclusively considering the chelating action of dithiocarbammates. In fact the chelating of zinc, a metal which is present in the prosthetic group of alkaline phosphatasis, can be carried out placing the serum enzymes in the presence of growing concentrations of dithiocarbamates. The concentration of dithiocarbamates that is able to determine the complete inactivation of the enzymes is high, equal to 8 mg/ml.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMedDate not supplied

[Surveillance of health status in an agrarian environment: proposal for a method. 2. Environmental data].

In this second note, the Authors consider the environment surrounding the farms to identify the agricultural practices affecting both the ecological bicycle and the health of the farm-hands. The risk factors in the farm are principally the use of agricultural chemicals (pesticides, fertilizers, nitroso-compounds, etc.) and quality of the irrigation and drinkable water. In the first phase of the survey a complete analysis of environment was carried out to: a. identify all sources of pollution such as industries, roads, etc. b. consider drinkable water supplies, wastewater disposal and hygienic conditions in houses. At the same time data were collected about the use of pesticides, fertilizers and other agricultural chemicals, the characteristics of irrigation water, the presence of animals, storehouses, garages, etc. In the second phase of the survey a quality analysis of drinkable and irrigation water was carried out; the presence of dangerous chemicals (amines, nitrosoamines, nitrites, nitrates) in the vegetable caused by agricultural practices was also verified. The results demonstrated a substantial good hygienic situation of the farms but a bad state of drinkable and irrigation waters. We have difficulty in finding out how much and how the pesticides were used; therefore it will be necessary to control these practices more carefully. The amount of nitrites and nitrates in vegetables was normal, while no amines and nitrosoamines were found. The results suggest that it will be necessary in the future both to estimate the pesticide residues on the vegetables and the amount of fertilizers in the soil, and to analyse the soil composition.

Adult↗
PubMed1989

Preventive action of vitamin C on nitrosamine formation.

N-Nitroso compounds are known to form endogenously in the human stomach from the precursors nitrite as well as secondary and tertiary amines. Ascorbic acid has been found to be an effective blocking agent for this process of formation of carcinogenic substances, both in vitro and in vivo. The mechanism by which ascorbic acid reacts is chemical in nature and results in the formation of NO and dehydroascorbic acid. Since NO can be recycled in the presence of O2 to form [NO]x, which is capable of additional nitrosation, greater than stoichrometric amounts of ascorbate are required for effective inhibition in vivo. The efficacy of ascorbic acid for inhibition of nitrosamine formation in humans has been demonstrated both clinically and epidemiologically through the use of "Nitrosoproline Test"--of Ohshima and Bartsch.

Ascorbic Acid↗
PubMed1989

[Synthesis of N-2-methylpropyl-N-1'-methylacetonylnitrosamine and its physical properties].

N-2-methylpropyl-N-1'-methylacetonylnitrosamine (NMAMPA) is a new N-nitroso compound found in natural moldy millet and wheat flour from Linxian county, Henan Province. The volatile nitrosamine is mutagenic in several short-term biological assays, and so we proceeded to synthesize larger amounts for the study of carcinogenesis. The main steps were as follows: 1) preparation of 3-bromobutanone (I) by bromination of butanone, 2) alkylation of 3-bromobutanone (I) with isobutylamine to give the secondary amine (II), and 3) nitrosaton of secondary amine (II) with sodium nitrite to yield NMAMPA (III). NMAMPA is a pale yellow liquid which is slightly soluble in water and freely soluble in ether, chloroform and dichloromethane. At room temperature, NMAMPA slowly turns brown, and decomposition takes place after prolonged exposure to UV light. A dilute solution of NMAMPA may be degraded in a freezer at 4 degrees to 6 degrees C.

Carcinogens↗
PubMed1989

[Carcinogenic hazard of nitrosodimethylamine in humans].

Literary data on the evaluation of carcinogenic hazard of nitroso compounds and in particular nitrosodimethylamine (NDMA) were analyzed. Their hazardous impact on humans was confirmed. The study results enabled one to set the total safety dose of NDMA at 0.1 mg per animal, to determine NDMA safety levels in environment, i.e., atmospheric air and water reservoirs, at. 0.0001 mg/m3 and 0.0001 mg/l, respectively, and to establish the total human safety level of NDMA at less than 0.002 mg per day.

Air Pollutants↗
PubMed1989

[Esophageal carcinoma in human fetus induced by N-methyl-N-benzylnitrosamine (NMBzA)].

Previous studies have suggested that N-nitroso compounds play a causative role. In the present study, human fetal esophageal epithelium was cultured for 3 weeks with NMBzA obtained in Linxian County (a high incidence area of esophageal cancer). Then, the explants were heterotransplanted to mesentery of BALB/c nude mice which were continually fed with NMBzA in drinking water for 8 months. The results showed that in NMBzA-treated mice, a small tumor was found on the mesentery two months after transplantation. The small tumor gradually grew to 2 x 1.8 cm in size 8 months after transplantation. No tumor was observed in control nude mice. Macroscopically, no tumor was seen in the esophagus of nude mice bearing esophageal tumor on mesentery. Pathology of the induced tumor showed squamous cell carcinoma. DNA extracted from the tumor induced by NMBzA was hybridized with Alu sequence using dot blot. Alu sequence was present in the induced tumor, indicating that the tumor is of human origin. This is the first report to confirm that human esophageal carcinoma could be induced by N-nitrosamine. It provides a direct evidence that NMBzA is a causative agent of esophageal cancer in Linxian County.

Animals↗
PubMed1989

Effects of the intake of selected vitamins and minerals on cancer prevention.

This paper provides an overview of our knowledge on the involvement in cancer of vitamins A, C and E and of calcium, selenium and zinc. This work is a background for studies on dietary magnesium's effects on cancer. Consumption of vitamin A and its dietary precursors has been associated with reduced cancer at several sites in human and animal studies. Carcinogenesis studies using several models of cancer have been conducted on the influence of vitamin A deficiency, vitamin A excess and supplementation of vitamin A analogues. Vitamins C and E are effective in the prevention of N-nitroso compound (nitrosamine) formation. Vitamin C is effective in aqueous and vitamin E is effective in non-aqueous media. Both of these vitamins also have inhibited carcinogenesis by preformed carcinogens at several sites, but enhancement has been observed at some sites when excess vitamin treatment was studied. The potential role of calcium in the prevention of colon cancer is being pursed. Few experimental studies have been conducted but data support an effect of calcium on colonic epithelial proliferation. Epidemiological and especially experimental results suggest an inhibition of cancer by dietary selenium. In animal studies, selenium supplementation has been particularly effective in inhibiting colon and mammary carcinogenesis, but enhanced carcinogenesis was observed in some studies on skin, liver and pancreas cancer. Data suggest that zinc deficiency may be a factor in esophageal cancer; however, studies on tumor growth have demonstrated retarded tumor growth in zinc-deficient animals.

Animals↗
PubMed1989

[Nitrate and nitrite in the urine, saliva and blood of urologic patients].

Nitrate and nitrite contents were determined in urine, saliva, and blood of 298 patients suffering from urological diseases. Crude values of nitrate and nitrite in morning urine without any correction due to density and creatinine are sufficient for epidemiological purposes. Significant correlations exist with vegetables intake and bacteriuria, but not with age, sex, disease, smoking, and medicaments. Neither nitrate nor nitrite may be considered to be general indicators of inflammatory processes in the urogenital tract. According to recent investigations nitrite formation during bacterial infections must be seen in connection with simultaneously occurring macrophage activation, as the latter one is catalyzing the formation of carcinogenic N-nitroso compounds from nitrite and secondary amines.

Escherichia coli Infections↗
PubMed1989

[The effect of Chinese teas on the occurrence of oesophageal tumor caused by N-nitrosomethylbenzylamine in rats].

Five groups of rats were given different varieties of Chinese tea as drinking water and on additional two groups of rats were given water with or without N-nitrosomethylbenzylamine (NMBzA) as controls. Except the control group, all the animals were intubated with NMBzA (5 mg.kg-1/wk) for 6 or 12 weeks. After 6 weeks, the incidence of oesophageal mucosa lesions was significantly lower in the tea-treated rats (16-59%) than the control group with NMBzA (100%). After 12 weeks, the incidence of oesophageal tumor was also significantly lower in the tea-treated groups (42-67%) than the control group with NMBzA (90%). Similar results were obtained in the tumor size and the number of tumors developed. The anti-carcinogenic effects of the 5 varieties of Chinese tea were also not the same the Fujian Oolong tea and Jasmine tea had the strongest effect. The results suggest that Chinese tea can inhibit the carcinogenesis caused by N-nitroso compound.

Animals↗
PubMed1989

[Potential risk of pharmacologically induced hypochlorhydria in the treatment of peptic ulcer disease].

The introduction of the very potent anti-secretory ulcer-healing drugs that effectively inhibit gastric acid secretion actualized the problem of pharmacologically induced hypochlorhydria. Potential dangers of hypochlorhydria relate mainly to the observation that various microorganisms normally destroyed by gastric acid survive and proliferate in the stomach and small intestine and thus increase the risk of the serious gastrointestinal infections. It has been also suggested that the proliferation of the intragastric bacteria may convert dietary nitrate into nitrite that may be nitrosated to carcinogenic N-nitroso compounds. Increased risks of nosocomial pneumonia or acute stress bleeding in ventilated intensive care unit patients become additional hazards during the treatment with antisecretory agents. Moreover, there is now evidence that after a course of treatment with antisecretory agents peptic ulcer recur more rapidly. Obviously, enthusiasm resulting of the great efficacy of antisecretory drugs in promoting ulcer healing must be hampered by previous considerations.

Anti-Ulcer Agents↗
PubMed1989

Effects of postnatal administration of tumour-promoting barbiturates on the development of tumours initiated by prenatal exposure of fetal rats and mice to N-alkylnitrosoureas.

Prenatal administration of chemical carcinogens followed by postnatal application of tumour promoters can result in tumour formation at sites where no tumours would occur in the absence of promotion. Three different epithelia in mice and rats have been shown to be susceptible to transplacental initiation by N-nitroso compounds or polynuclear aromatic hydrocarbons, yielding potentially neoplastic cells in fetal tissues which can remain latent indefinitely until stimulated to proliferate by postnatal exposure to a promoting agent. These include epidermal squamous epithelium in mice, renal cortical epithelium in mice, and thyroid follicular epithelium in both mice and rats. The fact that effective promoters of carcinogenesis in nonsquamous epithelia include drugs such as phenobarbital that are administered to humans in high doses for prolonged periods suggests that prenatal initiation followed by postnatal promotion may pose significant risks for humans, and should be considered in designing epidemiological searches for etiological factors that contribute to the incidence of epithelial tumours in man.

Aging↗