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Biomedical subjects

H F Stich

Publications and source records attributed to H F Stich.

At least 73 records · Page 4Linked to original sources
PubMed1982

The inhibitory effect of whole and deproteinized saliva on mutagenicity and clastogenicity resulting from a model nitrosation reaction.

The objective of this study was to simulate in vitro at least some of the conditions that prevail in man during ingestion of nitrate and nitrosable compounds. Human saliva has been chosen because most chemicals ingested through food will interact with saliva. The nitrosation of methylurea was used as a model because the nitrosation products can be readily detected by their mutagenic (his+ revertants of S. typhimurium) and clastogenic (chromosome aberrations in CHO cells) properties. The results show that human saliva inhibits the formation of mutagenic and clastogenic nitrosation products when present during nitrosation. A 50% inhibition of mutagenicity results from the addition of a saliva sample diluted at 5% of the original concentration. In the test system used a similar inhibitory effect was obtained by 2.5 mM ascorbic acid or 2.0 mM chlorogenic acid. The main inhibitory agents seem to reside in a deproteinized fraction which was filtered through an ultrafilter UM2 (greater than 1000 MW). At strong acid levels (below pH 2) the saliva loses its inhibitory effect on the nitrosation of methylurea. The contribution of saliva to the inhibition of endogenous nitrosation within the oral cavity or stomach is discussed.

Biotransformation↗
PubMed1982

Induction of mitotic gene conversion by browning reaction products and its modulation by naturally occurring agents.

Mitotic gene conversion in the D7 strain of Saccharomyces cerevisiae was significantly enhanced by exposure to non-enzymatic browning reaction products. These products were formed during the heating of sugar (caramelization reaction) or sugar-amino acid mixtures (Maillard reaction) at temperatures normally used during the cooking of food. Several modulating factors of this convertogenic activity were identified. These factors included two main groups: (1) trace metals which are widely distributed in the environment; and (2) several cellular enzymatic systems. The convertogenic activities of a heated glucose-lysine mixture and a commercial caramel powder were completely suppresses when yeast were concurrently exposed to these products and to either FeIII or CuII. Equimolar concentrations of MnII or sodium selenite had no effect on the convertogenic activity of the products of either model system. Horse-radish peroxidase, beef liver catalase and rat liver S9 preparations each decreased the frequency of gene conversion induced by the caramel powder and the heated glucose-lysine products. This modulating activity of the enzymes was lost if they were heat-inactivated. These studies indicate the presence of a variety of protective mechanisms which can modify genotoxic components in complex food mixtures.

Amino Acids↗
PubMed1982

Antimutagenic activity of browning reaction products.

The Salmonella typhimurium assay was used to determine the antimutagenic effect of products of 2 non-enzymatic browning reactions obtained by heating a lysine-fructose mixture at 121 degrees C for 1 h and by carmelizing D-sucrose at 180 degrees C for 1.5 h. The antimutagenic effect was tested by exposing strain TA1535 in suspension to N-methyl-N' -nitro-N-Nitrosoguanidine (MNNG) in the presence of the browning reaction products. In the case of aflatoxin B1, strain TA98 was used and the browning reaction products were added to the precarcinogen and an S9 mixture. The mutagenic activity of both carcinogens was significantly suppressed by the browning reaction products.

Aflatoxin B1↗
PubMed1981

A comparative genotoxicity study of chlorogenic acid (3-0-caffeoylquinic acid).

Chlorogenic acid, a compound which occurs naturally in many food items, was assayed for genotoxic activity in 3 different test systems: reverse mutations in the preincubation test with Salmonella typhimurium, gene conversion with Saccharomyces cerevisiae strain D7, and chromosome aberrations in Chinese hamster ovary (CHO) cells. Chlorogenic acid was directly convertogenic and clastogenic, but lacked a mutagenic capacity in the Salmonella bioassay. The transition metal Mn2+ enhanced the clastogenic and convertogenic activity of chlorogenic acid. In the presence of Mn2+ (10(-4)M), chlorogenic acid increased the frequency of his+ revertants in TA98 and TA100 strains of S. typhimurium. Caffeic acid and, to a lesser degree, quinic acid, which are components of chlorogenic acid, also showed genotoxic activity. The results show the importance of using several assays in combination with transition metals when testing for genotoxicity.

Animals↗
PubMed1981

Potentiation of genotoxicity by concurrent application of compounds found in betel quid: arecoline, eugenol, quercetin, chlorogenic acid and Mn2+.

5 components of the betel quid were examined for their clastogenic activities individually and in various combinations. They included the alkaloid, arecoline, from the betel nut (Areca catechu L.), eugenol, from the betel vine (Piper belle L.), chlorogenic acid, from tobacco leaves (Nicotiana tabacum), quercetin, from fennel seeds (Foeniculus vulgare Mill.) and the ubiquitous transition metal Mn2+. The clastogenic effects of the concurrent applications of arecoline plus eugenol, arecoline plus quercetin and arecoline plus chlorogenic acid were greater than the sum of the action of each individual component. Similarly, the combinations of arecoline, chlorogenic acid and Mn2+ induced frequencies of chromosome aberrations which exceeded the sum of the clastogenic activities of individually applied compounds or the sum of the clastogenic activities of 2 jointly applied compounds (arecoline plus Mn2+, or chlorogenic acid plus Mn2+). The clastogenic activity was estimated as the frequency of metaphase plates with at least 1 chromatid break or chromatid exchange, or the average number of chromatid breaks and exchanges per Chinese hamster ovary (CHO) cell. A potentiating (enhancing) action was also evident when 2 clastogens were used at doses which would not lead to a detectable increase in the frequency of chromosome aberrations when applied individually. It may be useful to distinguish between a "genotoxic range", which would be applicable to individually assayed compounds, and a "cogenotoxic range", which may include concentrations at which a chemical exerts a potentiating effect when combined with other genotoxic or non-genotoxic compounds.

Animals↗
PubMed1981

Clastogenic activity of caramel and caramelized sugars.

Cultured Chinese hamster ovary (CHO) cells were exposed for 3 h to caramelized solutions of the sugars sucrose, glucose, mannose, arabinose, maltose and fructose. Each of these caramelized sugars induced a relatively high frequency of chromosome breaks and exchanges in the treated cells. The non-caramelized sugars did not increase the frequency of chromosome aberrations. A potent clastogenic effect was also observed when a commercially used caramel powder was assayed. Up to 54% of all examined metaphase plates of the treated CHO cells had at least one chromosome break or exchange. This chromosome-damaging action of commercial caramel powder was reduced in the presence of liver microsomal (S9) preparation or FeII and FeIII. The transition metals CuII and MnII neither enhanced nor reduced the clastogenic activity of the caramel powder.

Animals↗
PubMed1981

Clastogenic activity of dried fruits.

The clastogenic activities of several commercially-dried fruits, including black and golden-seedless raisins, medium-sized California prunes, table dates, bananas, California black mission figs and breakfast apricots, were examined using Chinese hamster ovary (CHO) cells as the test organism and chromosome aberrations as the endpoint. Treatment of the CHO cells with water extracts of these dried fruits significantly increased the frequencies of metaphase plates with 1 chromosome break or exchange as well as the average number of chromosome exchanges per metaphase plate. A liver microsomal S9 mixture reduced this clastogenic activity. Dried fruits represent an example of widely consumed food products with strong genotoxic activities.

Animals↗
PubMed1981

Clastogenicity of furans found in food.

Cultured Chinese hamster ovary (CHO) cells were exposed for 3 h to furan and 6 furan derivatives (furfural, furfuryl alcohol, 5-methyl furfural, 2-methyl furan, 2,5-dimethyl furan and 2-furyl methyl ketone). Each of the 6 furan derivatives induced a relatively high frequency of chromatid breaks and chromatid exchanges in the absence of a liver microsomal activation preparation. The response of the furans to the addition of an S9 mixture differed. The clastogenic activities of 5-methyl furfural, 2-furyl methyl ketone, furfural and furfuryl alcohol were increased, whereas that of 2-methyl furan and 2,5-dimethyl furan were significantly decreased. Furan itself showed a clastogenic activity only in the presence of an S9 mixture.

Animals↗
PubMed1981

The action of transition metals on the genotoxicity of simple phenols, phenolic acids and cinnamic acids.

Simple phenols (catechol, 4-methyl catechol, resorcinol, phloroglucinol and pyrogallol), phenolic acids (p-hydroxybenzoic acid, protocatechuic acid, vanillic acid, gallic acid, syringic acid and salicylic acid), a phenylacetic acid (3,4-dihydroxyphenylacetic acid) and eugenol were assayed for clastogenic activity in Chinese hamster ovary (CHO) cells with and without the addition of a n S9 mixture, Cu2+ (10-4M) and Mn2+ (10-4M). All dihydroxylated and trihydroxylated phenolics induced chromatid breaks and exchanges. The introduction of a methyl group seems to reduce the clastogenic capacity. The addition of an S9 mixture or the transition metals Cu2+ and Mn2+ enhanced the chromosome-damaging activity in some phenolics and suppressed it in others.

Animals↗
PubMed1981

Chromosome-damaging activity of ferritin and its relation to chelation and reduction of iron.

Ferritin from horse spleen was found to cause severe chromosome aberrations in cultured Chinese hamster ovary cells. Ferritin at 15 to 170 microgram/ml was clastogenic and at higher doses was cytotoxic. At comparable concentrations of protein or iron, neither apoferritin nor complexed iron was clastogenic. Sulfhydryl compounds glutathione and cysteine reduced the cytotoxic and clastogenic activities of ferritin. Physiological concentrations of glutathione may normally be sufficient to protect cells from damage. The reducing agent ascorbate had little protective effect. Chelating agents varied in their inhibitory activity: ethylenediaminetetraacetic acid (hexadentate) greater than nitrilotriacetic acid (tetradentate) greater than salicylate (bidentate). 2,2'-Bipyridyl enhance the chromosome-damaging action of ferritin while histidine did not markedly alter the frequencies of aberrations. Catalase and superoxide dismutase showed no inhibitory activity. The mechanism of DNA damage may involve reduction of Fe(III) in the ferritin core to Fe(II), followed by reoxidation of Fe(II) with possible formation of free radicals.

2,2'-Dipyridyl↗
PubMed1980

Mutagenicity of fecal extracts from carnivorous and herbivorous animals.

Extracts of the feces of 3 carnivorous animals (dog, river otter and sea gull) and 5 herbivorous animals (cow, horse, sheep, chicken and goose) induced chromosome aberrations (breaks and exchanges) in cultured CHO cells. The addition of CuII (10(-4)M) enhanced the clastogenic effect of fecal extracts of the examined animals with the exceptiion of 1 dog and 3 cow samples. Catalase reduced the chromosome-breaking and mitosis-inhibiting capacities of fecal extracts. These results indicate the presence of hydrogen peroxide-forming compounds. The possibility must be considered that animal and human excreta may be a major source of mutagens entering man's environment.

Animals↗
PubMed1980

Unscheduled DNA synthesis and chromosome aberrations induced by inorganic and organic selenium compounds in the presence of glutathione.

Glutathione strongly enhanced the induction of unscheduled DNA synthesis (UDS) in cultured human cells by inorganic selenium compounds: sodium selenate, sodium selenite and sodium selenide. In the presence of 10(-3) M glutathione, high levels of UDS (74-114 grains per nucleus) were observed in cells treated with (i) selenate at 10(-3) M, (ii) selenite at 10(-5)-3 X 10(-4) 7, and (iii) selenide at 10(-5)-10(-3) M. Glutathione at 10(-3) M also enhanced the clastogenic and cytotoxic effects of selenite and selenate in Chinese hamster ovary (CHO) cells. Glutathione at 10(-4) M or 10(-2) M caused less enhancement of DNA damage and toxicity in both the UDS and chromosome aberration assays. In the absence of glutathione, these inorganic selenium compounds induced low levels of UDS (up to 13 grains per nucleus) and moderate frequencies of chromosome aberrations (up to 11%). 3 organic selenium compounds (selenocystine, selenocystamine and selenomethionine) were also examined for the induction of UDS. No unscheduled DNA synthesis was detected in cells treated with selenocystamine or selenomethione, with or without added glutathione. However, selenocystine alone at 10(-4)-10(-3) M induced a low level of UDS; glutathione enhanced the DNA-damaging effect of selenocystine. The maximum amount of UDS (22 grains/nucleus) occurred in the presence of 10(-2) M glutathione. This was about one-fifth of that detected in cells treated with inorganic selenium compounds and 10-fold lower concentrations of glutathione (10(-3) M). The results suggest that recution is involved in the conversion of selenium compounds to mutagenic forms. The active mutagens may be selenols, GS-Se- from inorganic selenium and R-Se- from organic selenium compounds.

Animals↗
PubMed1980

Mutagenic activity of ascorbate in mammalian cell cultures.

Exposure of Chinese hamster ovary (CHO) cells to solutions of ascorbate (2--5 x 10(-4) M) resulted in the induction of somatic mutations at the hypoxanthineguanine phosphoribosyl transferase (HGPRT) locus. Mutant cells were resistant to 6-thioguanine (10 microgram/ml) and sensitive to HAT (hypoxanthine, aminopterin, thymidine) medium. Doses of ascorbate which were mutagenic were also toxic. Addition of catalase to such ascorbate concentrations prevented both mutagenesis and toxicity. This suggests that mutagenic metabolites of ascorbate may involve peroxide radicals.

Animals↗