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Biomedical subjects

H F Stich

Publications and source records attributed to H F Stich.

At least 55 records · Page 3Linked to original sources
PubMed1984

Use of the micronucleus test to monitor the effect of vitamin A, beta-carotene and canthaxanthin on the buccal mucosa of betel nut/tobacco chewers.

The frequency of exfoliated cells with micronuclei in buccal swabs was used to estimate the protective effect of vitamin A, beta-carotene and canthaxanthin (4,4'-diketo-beta-carotene) on the buccal mucosa of betel (areca) nut/tobacco chewers. Micronuclei were scored on exfoliated cells taken by swabbing and stained with the Feulgen reaction and fast green. The betel (areca) nut/tobacco chewers served as their own controls. Prior to the administration of vitamin A and beta-carotene, the examined betel quid chewers had elevated frequencies of micronucleated buccal mucosa cells, averaging 4.03% +/- 1.24 SD (n = 26) and 3.43% +/- 1.22 SD (n = 25), respectively. The frequency of micronucleated buccal mucosa cells in non-chewers and non-smokers was 0.51% (n = 52). Following a 9-week ingestion of vitamin A (150,000 IU/week) and beta-carotene (180 mg/week in 6 capsules), the frequency of micronucleated cells decreased significantly (p less than 0.001) to 1.70% and 1.16%, respectively. No significant shift in the frequencies of micronucleated cells was observed following the intake of canthaxanthin (180 mg/week in 6 capsules) for 9 weeks or that of a placebo. The lack of protective activity of canthaxanthin, which is a good trapper of oxygen singlets but cannot be converted into vitamin A, suggests that vitamin A and beta-carotene exert their inhibitory effect on the formation of micronuclei by a mechanism not involving the scavenging of free radicals. The efficacy of beta-carotene as an inhibitor of micronucleated cell formation, the lack of toxicity, and its availability from a multitude of dietary sources should focus attention on this carotenoid as a promising chemopreventive agent.

Adult↗
PubMed1984

Reduction with vitamin A and beta-carotene administration of proportion of micronucleated buccal mucosal cells in Asian betal nut and tobacco chewers.

The frequency of micronuclei in cells scraped from inside the human cheek is a measure of chromosome breakage in earlier cell divisions, and it can be increased tenfold by carcinogenic stimuli. Supplementation for 3 months of the diet of 40 rural Filipino betel chewers with sealed capsules of retinol (100 000 IU/week) and beta-carotene (300 000 IU/week) was associated with a threefold decrease (from 4.2% to 1.4%) in the mean proportion of cells with micronuclei. This proportion decreased in 37 of the 40 supplemented subjects and no large increases were seen in any subjects. In 11 unsupplemented betel chewers in a nearby cluster of houses the mean proportion of micronuclei did not change (4.3% before and 4.8% three months later). This suggests the possibility that in this population an increase in the dietary intake of retinol and/or carotene may reduce the incidence of oral cancer, which is an important neoplasm in many parts of Asia.

Adult↗
PubMed1984

The effect of dietary factors on nitrosoproline levels in human urine.

The effect of dietary components on the levels of nitrosoproline ( NPRO ) excreted over a 24 h period in the urine was examined in volunteers ingesting known amounts of various food products. The ingestion of nitrite-preserved meats (85-170 g per meal), including canned, rolled or Yunnan ham, cured pork, luncheon meat, and various Chinese and European-style sausages, led to urinary NPRO excretion levels ranging from 2.5 to 78.5 micrograms/24 h, whereas the consumption of non-preserved meat and fish products, including chicken, herring, salmon, shrimp, ground beef (hamburger), pork chops and beef liver, led to relatively low NPRO excretion levels, ranging from 0.0 to 0.8 micrograms/24 h. The urinary NPRO levels of 22 vegetarians and 14 lacto-vegetarians averaged 0.8 and 1.4 micrograms/24 h, respectively. A change from a nitrite-preserved meat diet to a vegetarian diet was accompanied by an approximately six-fold reduction in urinary NPRO levels; however, these remained above control levels for at least 3 days following the dietary change. The relatively high NPRO levels following the ingestion of nitrite-preserved meats could not be reduced by nitrite-trapping chemicals, including ascorbic acid, ferulic acid, caffeic acid, or phenolic-containing mixtures such as coffee and tea, which were effective in suppressing endogenous NPRO formation following the intake of nitrate and proline. The high urinary NPRO levels after ingestion of preserved meat products appear to be due to the consumption of preformed NPRO . An understanding of the relative contribution of preformed and endogenously formed nitrosamines appears to be essential when designing dietary intervention programmes.

Adult↗
PubMed1984

Comparison of DNA-repair synthesis, chromosome aberrations and induction of micronuclei in cultured human fibroblasts, Chinese hamster ovary and central mudminnow (Umbra limi) cells exposed to chemical mutagens.

In mammalian cells it has previously been observed that low DNA-repair activity is correlated with high chromosome-aberration frequency. Since fish cells typically express comparatively low amounts of DNA repair, the chromosome aberration test holds potential as a sensitive fish genotoxicity assay. A comparison of in vitro DNA-repair activity showed HF greater than CHO greater than Ul-H = Ul-F following exposure to MNNG and 4NQO. Although peak chromosome-aberration frequency varied CHO greater than Ul-H greater than HF, at comparable mutagen concentrations the relationship was Ul-H greater than HF greater than CHO following 4NQO exposure and Ul-H greater than HF = CHO after MNNG exposure. Analyzing for chromosome aberrations at high mutagen concentrations was not possible due to mitotic inhibition/toxicity which varied according to the mutagen and cell line. Micronuclei frequency varied CHO greater than Ul-H greater than HF = Ul-F. In CHO and Ul-H, a 10-15-fold increase over controls compares with only a 2-3-fold increase for HF and Ul-F. These differences are likely related, in part, to the cell-division rate of each line and the coincident repair of the damaged DNA. Reasons for the lack of negative correlation between DNA repair and chromosomal damage in fish cells are discussed.

Animals↗
PubMed1984

Determination of free and protein-bound N-nitrosoproline in nitrite-cured meat products.

Levels of nitrosoproline (NPRO) in the urine of subjects on a Western-style free-choice diet typically ranged from 1 to 2 ng/ml. Higher levels of NPRO in the urine were associated with the consumption of nitrite-cured meat products. The elevation in NPRO excretion after the consumption of cured meats was not diminished by the concurrent consumption of the nitrosation inhibitor ascorbic acid, indicating the presence of preformed NPRO or some NPRO precursor in the meat. Cured meat samples were analysed for NPRO using methanolic extraction, followed by gas chromatography and nitrosamine quantification by means of a thermal energy analyzer. Levels of NPRO detected in meats were less than those indicated by the amount of NPRO excreted when the same meat was eaten. Digestion of meat samples by proteolytic enzymes sharply increased the amount of NPRO detectable by chemical analysis. Nitrite-cured meat products contained 39-3900 ng total NPRO/g product. Of this amount of NPRO, 3-93% was protein-associated and only detectable after proteolytic digestion. Protein-associated NPRO may represent nitrosated N-terminal proline in proteins or peptides. Such NPRO would not be detectable as free NPRO on direct chemical analysis, but would be released by proteolysis in the digestive tract when the meat is eaten.

Adult↗
PubMed1984

Micronuclei in exfoliated human cells as a tool for studies in cancer risk and cancer intervention.

The use of the micronucleus test on exfoliated cells as an approach to identify genotoxic damage in human tissues which are targets for organ-specific carcinogens and from which carcinomas will develop, is described. Chromosomal damage by carcinogens to dividing basal cells of the epithelium results in the production of micronuclei in the daughter cells which migrate up through the epithelium and are exfoliated. Exfoliated cells can be readily obtained from several tissues, including the oral buccal mucosa (scrapings of oral cells), bronchi (sputum), urinary bladder and ureter (centrifugation of urine), cervix (smears) and esophagus (imprints from biopsies). The micronucleus test on exfoliated cells has been successfully used to: (1) recognize population groups at an elevated risk for cancer of the oral cavity or urinary bladder; (2) estimate synergistic or additive effects of carcinogen exposure (cigarette smokers plus drinkers of alcoholic beverages); (3) pinpoint the site within an organ from which most carcinomas will develop (oral cancers among 'inverted' smokers in the Philippines). The possibility that this assay may also serve as a rapid monitor for chemopreventive agents is suggested by a preliminary trial on the effect of vitamin A/beta--carotene dietary supplementation among 33 betel quid chewers in the Philippines. These individuals received sealed capsules of retinol (100,000 IU/week) and beta-carotene (300,000 IU/week) for a 3-month period. At the end of this time, the frequencies of micronucleated buccal mucosa cells were reduced from an average of 4.2% to 1.4%. No changes were observed in micronucleus frequencies among 11 betel quid chewers not receiving vitamin pills. Non- chewers of betel quid in this population had a micronucleus frequency of 0.5%.

Areca↗
PubMed1984

DNA repair synthesis following exposure to chemical mutagens in primary liver, stomach, and intestinal cells isolated from rainbow trout.

DNA repair synthesis was autoradiographically measured in liver, stomach, and intestinal cells isolated from rainbow trout which were exposed in vitro to the chemical mutagens, N-methyl-N'-nitro-N-nitrosoguanidine, 4-nitroquinoline 1-oxide, and aflatoxin B1. The level of repair was greatest in primary hepatocytes which responded to all three mutagens. Only nominal amounts of repair were detected in stomach cells following N-methyl-N'-nitro-N-nitrosoguanidine and 4-nitroquinoline 1-oxide exposures and in intestinal cells following 4-nitroquinoline 1-oxide exposure. In comparison with cultured rainbow trout cells, the quantity of DNA repair found in primary cells is significantly less.

4-Nitroquinoline-1-oxide↗
PubMed1984

Dietary phenolics and betel nut extracts as modifiers of N-nitrosation in rat and man.

Polyphenolic compounds (PPC) isolated from betel nuts and some dietary PPC were examined for their modifying effects on N-nitrosation in vitro and in vivo. The formation of N-nitrosodiethylamine (NDEA) and N-nitrosoproline (NPRO) was either enhanced or inhibited by PPC from betel nuts, depending on (1) the structure of the PPC, (2) the pH of the reaction medium, (3) the relative concentrations of nitrite and PPC, and (4) the nature of the nitrosatable amino compounds. Both catalysis and inhibition of endogenous nitrosation of proline were observed in rats, although to a lesser extent than in vitro. Caffeic and ferulic acids, as well as the PPC-containing beverages tea and coffee, exerted inhibitory effects on endogenous formation of NPRO in two human subjects. These results demonstrate that PPC can modify the yield of endogenously formed N-nitroso compounds, and may thus effect the carcinogen burden in man.

Animals↗
PubMed1983

Quantitating the synergistic effect of smoking and alcohol consumption with the micronucleus test on human buccal mucosa cells.

The micronucleus test was applied to exfoliated cells of the buccal mucosa of four population groups: (A) non-smokers and non-drinkers of alcoholic beverages, (B) non-smokers but alcohol drinkers, (C) smokers but non-drinkers, and (D) smokers and drinkers. An elevated frequency of micronucleated buccal mucosa cells was observed only in group D (smokers and alcohol drinkers). When group D was subdivided according to the number of cigarettes smoked, the frequency of micronucleated buccal cells and the average number of micronuclei per cell appeared to depend upon cigarette consumption. An approximately eight-fold increase of micronucleated mucosa cells was seen among alcohol drinkers who smoked three or more packs of cigarettes per day, and an approximately 4.2-fold elevation was observed when one to two packs were consumed. Neither smoking alone of up to and over 60 cigarettes per day nor ethanol drinking alone of up to 1.21 per day led to a detectable elevation of micronucleated buccal mucosa cells. Whether the strong synergistic effect between smoking and alcohol consumption, as seen by the frequency of micronucleated buccal mucosa cells, is related to their synergistic effect in the induction of oral cancers is an intriguing but open question.

Adult↗
PubMed1983

An intestinal cell-mediated chromosome aberration test for the detection of genotoxic agents.

The use of rat-liver S9 in genotoxicity tests may not reflect true metabolism by whole cells, particularly cells of target organs. We have tested mucosal cells of the mouse small intestine for the capacity to mediate activation/inactivation of chemical carcinogens. Mucosal cells were isolated by pronase digestion. Three million cells were co-cultured with Chinese hamster ovary fibroblasts during a 3-h exposure to chemical clastogens. In the presence of the mucosal cells, aflatoxin B1 (100 microM) was activated to produce chromosome aberrations in 30% of Chinese hamster ovary cell metaphases. 4-Nitroquinoline 1-oxide was deactivated by intestinal cells, while benzo[a]pyrene and dimethylbenz[a]anthracene were not activated by the cells. The clastogenicity of the phenolic compounds caffeic acid (0.28 mg/ml) and clorogenic acid (0.25 mg/ml) was eliminated by the mouse intestinal preparation. The pyrrolizidine alkaloid monocrotaline was activated by intestinal cells. The results suggest the presence of specific activation and deactivation enzymes in the intestinal mucosa. The intestine cell-mediated chromosome aberration test could provide a means to measure tissue-specific activation and deactivation capabilities.

4-Nitroquinoline-1-oxide↗
PubMed1983

Clastogenic activity of caffeic acid and its relationship to hydrogen peroxide generated during autooxidation.

Caffeic acid is a clastogenic cinnamic acid found in a conjugated form in a variety of foods. The possibility that the biological activity of caffeic acid is due to hydrogen peroxide generated during its autooxidation in solution was investigated using chromosome aberrations in Chinese hamster ovary cells as a test system. Freshly prepared caffeic acid at pH 7.00 contained only traces of hydrogen peroxide, as assayed by the molybdate-catalyzed release of I-3. Such solutions exhibited clastogenic activity which could not be accounted for by the level of hydrogen peroxide present, and which was not significantly diminished by the addition of catalase or horseradish peroxidase. 3-day-old solutions of caffeic acid exhibited higher levels of hydrogen peroxide, and increased biological activity. In such solutions, the clastogenic activity was catalase-sensitive and could be entirely accounted for by the level of hydrogen peroxide present.

Animals↗
PubMed1983

DNA repair synthesis in cultured mammalian and fish cells following exposure to chemical mutagens.

Unscheduled DNA repair synthesis (UDS) was measured autoradiographically in HF, CHO, RTG, RTO, CH and FHM cells given a 3-h exposure to MNNG, 4NQO, NA2AAF and AFB1. All the chemicals produced a dose-response, the magnitude of which varied with the particular chemical and cell line. HF produced the greatest response, CHO less and the fish cell lines the least. The response of all fish cell lines was approximately equal for a particular chemical. A number of factors were investigated to account for the comparative differences in UDS response. The time course of repair in HF, CHO and RTG following a 3-h exposure to MNNG or 4NQO was the same. As S-phase nuclei were observed in control slides and the amount of repair following UV exposure varies HF greater than CHO greater than RTG, neither 3HTdR nor mutagen uptake is limiting. The observed results are discussed.

Animals↗
PubMed1983

Inhibitory effect of betel nut extracts on endogenous nitrosation in humans.

Extracts of betel nut (Areca catechu) were tested for their capacity to inhibit the endogenous formation of nitrosamines by measurement of the amount of urinary N-nitroso-L-proline (NPRO) following ingestion of sodium nitrate (300 mg) and L-proline (300 mg) by 2 volunteers. A water extract of the dried nuts, an ether extract containing mainly (+)-catechin and (-)-epicatechin, and a caffeine-precipitated n-butyl alcohol extract containing primarily proanthocyanidins (tannins) strongly reduced the endogenous formation of NPRO. An average of 14.7 and 10.9 micrograms NPRO (8 expts per individual) was excreted in the urine of the 2 volunteers over a 24-hour period following the intake of sodium nitrate and L-proline. The water extract and the proanthocyanidin (tannin)-containing extract, both of which contain the dose equivalent of one-quarter of a nut, reduced the excreted NPRO to background levels, which varied from 0.5 to 3.6 micrograms and from 0.6 to 2.1 micrograms (6 expts) in 24-hour urine samples from the 2 volunteers. These results may exemplify the way in which naturally occurring phenolics, which are ingested daily in relatively large quantities, could affect the endogenous formation of carcinogenic nitrosamines.

Anthocyanins↗
PubMed1982

Inhibitory effects of phenolics, teas and saliva on the formation of mutagenic nitrosation products of salted fish.

The objectives of this study were to simulate in vitro some of the conditions that may prevail in man during the ingestion of a meal and to quantitate the inhibitory effect of phenolics and phenolic-containing beverages on the formation of mutagenic nitrosation products. The test system consisted of nitrosating (pH 2, 1 h, 37 degrees C) an aqueous fraction of a salt-preserved Chinese fish (Pak Wik) with or without the inhibitors to be tested and estimating the frequency of his+ revertants per survivor of Salmonella typhimurium (strain TA1535). The phenolics and teas were added to the nitrosation mixture. Catechin, chlorogenic acid, gallic acid, pyrogallol and tannic acid suppressed the formation of mutagenic nitrosation products. The inhibitory efficiency was comparable to that of ascorbic acid. A Japanese, a Chinese and a Ceylonese tea also prevented the formation of mutagenic nitrosated fish products at doses which are usually consumed by man. Moreover, saliva exerted an inhibitory effect. The inhibitory effect was not additive when the phenolics or saliva were added concurrently to the nitrosation mixture. The possibility that phenolics are involved in the apparent chemopreventive effect of fruits and vegetables is discussed.

Animals↗
PubMed1982

Application of the micronucleus test to exfoliated cells of high cancer risk groups: tobacco chewers.

Powdered tobacco (Khaini tobacco) with the addition of lime is commonly used by the residents of Bihar, India. The tobacco/lime mixture is usually placed on the inner side of the lower lip within the gingivolabial groove. About 42% of the users keep it at the front, the rest move the tobacco towards the left or right side within the oral cavity. Carcinomas (so-called "Khaini cancers") develop mainly at the site where the tobacco is in close contact with the mucosa. Scrapings of the mucosa were taken at sites where the tobacco is kept, then smears were prepared, stained with the Feulgen reaction and fast green, and screened for micronuclei which indicate the occurrence of chromosome aberrations in the dividing cell population of the basal layer. An elevated frequency of cells with micronuclei was found in the oral mucosa of all 27 examined Khaini tobacco users (Munda and Santal tribes) compared to that of non-chewers of similar ethnic background and dietary habits. The induction of micronucleated mucosa cells seems to be due to genotoxic agents released from the tobacco/lime mixture. In vitro, an aqueous extract of the Khaini tobacco elicits chromosome aberrations and micronuclei in cultured human fibroblasts and Chinese hamster ovary (CHO) cells. No chromosome-damaging effect was observed following the application of lime or calcium hydroxide (Ca(OH)2). The micronucleus test on exfoliated cells can provide evidence of carcinogen exposure in the tissue from which cancers will develop. This approach combines all the advantages of in vitro short-term tests for genotoxic and carcinogenic agents with those of using an intact organism with all its defence mechanisms.

Adolescent↗
PubMed1982

Inhibition of mutagenicity of a model nitrosation reaction by naturally occurring phenolics, coffee and tea.

Several plant phenolics, one instant coffee, one instant decaffeinated coffee, one roasted coffee, one Japanese tea, one black Indian tea, and one Chinese tea were examined for their inhibitory properties on mutagenicity resulting from the nitrosation of methylurea. Mutagenicity was estimated as the number of his+ revertants per survivor of Salmonella typhimurium TA1535 which was exposed in suspension to the nitrosation mixtures and the modulating agents for 20 min. Tannic acid, gallic acid and chlorogenic acid suppressed the mutagenicity of the model nitrosation system at concentrations similar to or even lower than ascorbic acid. The three tested coffees and three tested teas exerted an inhibitory effect on the mutagenicity of the test system at doses at which they are consumed.

Chlorogenic Acid↗