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PubMed1987

Prevention of exposure to N-nitrosamines in the rubber industry: new vulcanization accelerators based on 'safe' amines.

Introduction of 'safe' amino components into traditional accelerator molecules could be an effective measure to prevent formation of carcinogenic N-nitroso compounds during rubber production. About 20 new derivatives of the dithiocarbamate and sulfenamide class, based on 'safe' amines, were synthesized and shown to be suitable for industrial application. Some of the corresponding N-nitrosamines were prepared and investigated for mutagenicity in Salmonella typhimurium TA1535. No or weak mutagenic potential was observed in most cases. The nitrosatability of five sulfenamides derived from 'safe' amines was determined and found to be substantially lower than that of a commercial sulfenamide accelerator tested under identical conditions.

Animals↗
PubMed1987

Pathobiological effects of aldehydes in cultured human bronchial cells.

Effects of the tobacco smoke-related aldehydes, i.e., acetaldehyde, formaldehyde and acrolein, have been investigated in cultured human bronchial epithelial cells and fibroblasts. As determined from loss of colony-forming efficiency of epithelial cells, acrolein is 200- and 5000-fold more toxic than formaldehyde and acetaldehyde, respectively. The aldehydes differ markedly in their potencies to induce terminal differentiation, as indicated by cessation of growth and enhanced formation of cross-linked envelopes. The cellular content of glutathione is markedly decreased by acrolein, whereas formaldehyde and acetaldehyde only slightly decrease glutathione levels. All three aldehydes produce DNA damage, as indicated by the formation of DNA single-strand breaks and DNA protein cross-links. Both formaldehyde and acrolein are weakly mutagenic in fibroblasts. In-vitro assays of O6-methylguanine-DNA methyltransferase (MMT) activity indicate that it is markedly inhibited by acrolein, and to a lesser extent by formaldehyde. However, formaldehyde significantly inhibits removal of O6-methylguanine (O6-meG) in N-methyl-N-nitrosourea (MNU)-exposed cells. Thus, the many biological effects induced by aldehydes include: inhibition of proliferation, enhanced cellular differentiation, thiol depletion, DNA damage, mutation and inhibition of DNA repair in human cells. Furthermore, we speculate that exogenous or metabolically generated aldehydes may increase the genotoxicity of N-nitroso compounds by the dual action of causing DNA damage and inhibiting the repair of promutagenic O6-meG DNA lesions in human cells.

Aldehydes↗
PubMed1987

Determination of N-nitrosamines in gastric juice and urine and a comparison of endogenous formation of N-nitrosoproline and its inhibition in subjects from high- and low-risk areas for oesophageal cancer.

Samples of gastric juice were collected from a high-risk area for oesophageal cancer in China and analysed for N-nitroso compounds. N-Nitrosodimethylamine (NDMA), N-nitrosodiethylamine (NDEA), N-nitrosomethylbenzylamine (NMBzA), N-nitrosopyrrolidine (NPYR) and N-nitrosopiperidine (NPIP) were identified in descending order of concentration. Several unknown compounds were also detected in the fasting gastric juice. A positive correlation was found between the amount of nitrosamines in gastric juice and the degree of severity of lesions of the oesophageal epithelium: the amounts of nitrosamines in gastric juice from subjects with a normal oesophageal epithelium were lower than those in subjects with marked dysplasia or carcinoma of the oesophagus. In addition, 1500 samples of 24-h urine were collected from various communes in six high-risk areas and two low-risk areas for this cancer in China and analysed for N-nitrosamino acids. Subjects in high-risk areas excreted higher levels than those in low-risk areas. Intake of L-proline resulted in marked increases in levels of urinary N-nitrosoproline (NPRO) in inhabitants from both high- and low-risk areas. Intake of moderate doses of vitamin C, alpha-tocopherol and zinc by high-risk subjects reduced the urinary levels of N-nitrosamino acids to those found in undosed subjects in low-risk areas, suggesting a rational basis for prevention in high-risk areas.

China↗
PubMed1987

High urinary excretion of nitrate and N-nitrosoproline in opisthorchiasis subjects.

About 50% of the population in some provinces of north-east Thailand are infested with liver fluke (Opisthorchis viverrini), and many develop cholangiocarcinoma subsequently. This study was designed to demonstrate possible endogenous formation of N-nitrosoproline (NPRO) in this population. Diet samples, saliva and urine were taken from subjects with and without liver fluke and analysed for nitrate and nitrite; urine was also analysed for NPRO. Nitrate and nitrite levels in saliva were higher in subjects with liver fluke than in those without; total nitrate and NPRO excretion was also higher in this group. Subjects with liver fluke may therefore be more heavily exposed to N-nitroso compounds than others, and may be at higher risk for cholangiocarcinoma.

Adult↗
PubMed1987

Intake of Cantonese-style salted fish as a cause of nasopharyngeal carcinoma.

Ho (1971) of Hong Kong first proposed consumption of Cantonese-style salted fish, a traditional food among southern Chinese, as a possible risk factor for nasopharyngeal carcinoma (NPC) in this high-risk population. Four case-control studies have examined Ho's hypothesis; all results are supportive. The most convincing evidence of a causal association between intake of salted fish and NPC derives from a recent case-control study of young Hong Kong Chinese. It is estimated that over 90% of NPC cases under age 35 in Hong Kong are due to intake of this food during childhood. Preliminary experimental data on Cantonese-style salted fish indicate that N-nitroso compounds may be involved in the carcinogenicity of this human food.

Adult↗
PubMed1986

The effects of various substituted hydrocarbons on two heme synthesis regulatory enzymes.

Benzene and some of its derivatives have been shown to cause alterations in heme and globin synthesis. Structure/activity relationships of the effects of substituted aromatic hydrocarbons on delta-aminolevulinic acid synthetase (ALAS) and ferrochelatase (FC) activities were studied. These enzyme systems were studied because they were regulatory and represented the initial and final enzymes in the biosynthesis of heme. Normal values for rat liver ALAS were 250-350 microM ALA/g protein/30 min, mean 293 microM/g +/- 44 (SD). Normal values for FC were 12-40 microM heme/g protein/45 min, mean 18 microM/g +/- 0.7 (SD). Nitrosonaphtholics inhibited ALAS activity an average of 49%; nitrosobenzenes, 48%; chloronitrobenzoic acids, 39%; phenol, 37%; nitrophenols, 22%; aminophenols, 16% and chlorophenols, 5%. Certain compounds inhibited FC activity: nitrosonaphtholics, 99%; chlorophenols, 56% and nitrosobenzenes, 3%. Some compounds that significantly inhibited ALAS activity enhanced FC activity, e.g. phenolic compounds and chloronitrobenzoic acids. The inhibitory effect may reflect a blockage of the active site of the enzymes and/or binding of a required substrate. The enhancing effect may be due to making the binding site of the heme pocket of the porphyrin more accessible to iron. These techniques may prove useful for assessing toxicity of pollutants in animal species.

5-Aminolevulinate Synthetase↗
PubMed1986

The effect of nass use and smoking on the risk of oral leukoplakia.

The results of a survey of a population with a high incidence of oral cancer are presented in this paper. A remarkably high proportion (41%) of the men surveyed used nass, which is a mixture of tobacco, lime, ash, and cotton oil. The prevalence of oral leukoplakia, lesions thought to be a precursor of oral cancer, was high in persons who used nass (12%) and who smoked cigarettes (15%), and highest among those men who both used nass and smoked (21%). It has been shown that nass use increases the frequency of micronucleated cells in the exfoliated sublingual cells. The clastogenic and genotoxic effect of nass revealed in the study could be attributed to the presence of tobacco-specific N-nitroso compounds. However, the results of chemical analysis, which has shown that nass contains relatively low levels of these compounds, suggest that the relatively strong genotoxic activity of nass could primarily be associated with other chemicals, possibly oxidized phenolics. Despite the uncertainty as to which of the chemicals contained in nass are involved in the etiology of oral cancer and what exactly are the mechanisms of nass-induced carcinogenesis, the results of this study suggest that in populations where nass is widely used, oral leukoplakia and, most probably, oral cancer are conditions that could be prevented by the elimination of nass use and cigarette smoking.

Aged↗
PubMedDate not supplied

[Nitrate-reducing microorganisms in milk products and human milk].

The quantitative determination of nitrate-reducing microorganisms in food is important because of their role in the formation of N-nitroso compounds and methemoglobin. The total counts of microorganisms and the counts of nitrate-reducing microorganisms were assayed in various milk products and in human milk by the method of the most probable numbers using nitrate broth medium. The mean value and standard deviation of the nitrate-reducing microorganisms were the following: in pasteurized milk 3.4 +/- 1.1 log/ml (in spring and summer 4.2 +/- 1.1, and in winter 2.8 +/- 0.6 log/ml), in kefir "Tallinn' 2.9 +/- 1.1 log/ml, in fat kefir 2.9 +/- +/- 0.7 log/ml, in sour milk 3.9 +/- 0.5 log/ml, in fresh milk 4.6 +/- 0.6 log/ml and in human milk 2.7 +/- +/- 1.1 log/ml. The amount of nitrate-reducing microorganisms in pasteurized milk of the spring-summer period and in fresh milk was significantly higher than in human milk. The mean count of nitrate-reducing microorganisms in human milk is regarded as a maximum permitted count of these organisms in milk for bottle-fed sucklings. For them and for atrophic gastritis patients pasteurized or fresh milk should be boiled.

Animals↗
PubMed1985

Synthesis of methylisoamylnitrosamine from isoamylamine by fungi (Fusarium moniliforme).

Methylisoamylnitrosamine, a carcinogenic N-nitroso compound, has been formed in glucose ammonium nitrate medium containing 150 mg of isoamylamine (a primary amine) inoculated with a common fungus (Fusarium moniliforme Sheldon), to which 400 mg NaNO2 are added after incubation for 7-8 days at 28 degrees C. No such compound has been found in control samples without fungi or isoamylamine. This paper reports a method of experimental synthesis of the nitrosamine by F. moniliforme strains 82-01 and 83-01, using isoamylamine and NaNO2, as well as the analysis of the compound by GC/MS and GC/TEA.

Amines↗
PubMed1985

Levels of O6-methylguanine acceptor protein in tissues of rats and their relationship to carcinogenicity and aging.

N-nitroso compounds react with cellular DNA to produce various damaging adducts, one of the more important being O6-alkylguanine. DNA restoration is accomplished by transfer of the alkyl group to a cysteine residue of an acceptor protein. The levels of acceptor activity were compared in several tissues from well-fed and dietary-restricted inbred SD rats 30-1,194 days of age. Striking and consistent differences were found in the levels of acceptor activity in different tissues from both groups; these levels corresponded to their sensitivity to tumorigenesis by alkylating agents. Acceptor activity levels were highest in the liver and somewhat less in the spleen; there were significantly lower levels in brain and kidney. The random loss with time in the integrity of DNA may cause alterations in cellular function or limit cellular proliferation, thus leading to senescence and death. DNA repair processes may alter the rate of accumulation of damage, thereby affecting potential longevity. There were no significant age-associated changes in the ability of cells from either dietary group to remove DNA adducts and there was no evidence of alterations in the acceptor protein with age that would compromise its functional activity.

Aging↗
PubMed1985

Nitrates: laboratory evidence.

Neither nitrate nor nitrite per se has been demonstrated to produce cancer in experimental animals. The potential carcinogenicity of either of these substances would appear to derive from their involvement in the production of carcinogenic N-nitroso compounds. The extent to which such compounds form has been the subject of numerous studies.

Animals↗
PubMed1979

Chronic toxicity of sodium nitrite in mice, with reference to its tumorigenicity.

Sodium nitrite has been widely used as one of the most effective food additives to tinge color on cured meat. However, it has been elucidated that this chemical is not merely a precursor of N-nitroso compounds, many of which are strongly carcinogenic, but also a mutagenic substance in biological tests. In order to ascertain the possible tumorigenicity of sodium nitrite itself, chronic toxicity of the agent in mice, by means of daily oral administration as drinking water for more than 18 months, in the concentration of 0.5 (maximum tolerated dose), 0.25, and 0.125%, was tested. As a result, development of various tumors, including thymic lymphoma, nonthymic lymphoid leukemia, pulmonary adenoma and carcinoma, and benign and malignant tumors in soft tissue, was seen in these mice. However, as to the incidence of tumors as well as the developmental time of each histologically classified tumor, no apparent difference was detected between those in the experimental groups and the control group.

Animals↗