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Biomedical subjects

H F Stich

Publications and source records attributed to H F Stich.

At least 91 records · Page 5Linked to original sources
PubMed1980

Enhancing and inhibiting effects of propyl gallate on carcinogen-induced mutagenesis.

The food additive propyl gallate has a significant effect on the mutagenic activities of several carcinogens as measured by the Salmonella/microsome mutagenesis assay. Propyl gallate (10(-2) to 10(-4) M) inhibits the mutagenic activites of the carcinogens N-methyl-N-'nitro-N-nitrosoguanidine (MNNG) and N-acetoxy-2-acetylaminofluorene (N-acetoxy-AAF). It also reduces the mutagenic effect of aflatoxin B1, a carcinogen which requires activation with a S-9 microsomal preparation. In contrast, propyl gallate at equimolar concentrations causes an enhancement of the mutagenic activities of the carcinogens N-hydroxy-2-acetylaminofluorene (N-hydroxy-AAF) and 4-nitroquinoline 1-oxide (4NQO). The enhancement of 4NQO-induced mutagenesis occurs with a range of 4NQO concentrations. Moreover, both frameshift (TA98) and base substitution (TA100) bacteria indicator strains demonstrate an enhanced mutagenesis to 4NQO in the presence of the propyl-gallate. Propylgallate alone has no effect on the spontaneous reversion rate of S. typhimurium to histidine propotrophy.

Biotransformation↗
PubMed1979

Chromosome breaking activity of human feces and its enhancement by transition metals.

Chloroform-methanol extracts from human fecal samples were found to contain compounds which induce chromosome aberrations in Chinese hamster ovary cells. The induction of chromosome aberrations is stimulated by Cu2+ or Mn2+ and inhibited by Fe2+ or Fe3+. Addition of catalase to the fecal extract or the mixture of fecal extract and Mn2+ reduced the frequency of chromosome aberrations. These properties are indicative of hydroxyradical producing agents.

Animals↗
PubMed1979

DNA damage and DNA repair in cultured human cells exposed to chromate.

DNA damage and DNA repair have been observed in cultured human skin fibroblasts exposed to potassium chromate but not to a chromic glycine complex. DNA repair synthesis (unscheduled incorporation of [3H]thymidine (TdR)) was measured in cells during or following exposure to chromate and was significant for chromate concentrations above 10(-6) M. Maximal DNA repair was observed at about 10(-4) M chromate. DNA repair capacity was found to be saturated at this concentration. Chromate was stable for at least 8 h in culture medium and produced approximately a linear increase in repair with duration of exposure. DNA damage as determined by alkaline sucrose gradient sedimentation was detected after treatment for 1.5 h with 5 . 10(-4) M chromate. Exposure to 10(-7) M chromate solution for 7 days inhibited colony formation while acute (1 h) treatment was toxic at 5 . 10(-6) M. The chromic glycine complex was toxic above 10(-3) M for a 1-week exposure but was not observably toxic after a 1-h treatment. These results indicate that chromate and not chromic compounds may be the carcinogenic form for man. The nature of the ultimate carcinogen is discussed. These findings illustrate the utility of the DNA repair technique to study the effects on human cells of inorganic carcinogens and mutagens.

Adult↗
PubMed1979

Sister chromatid exchanges induced in cultured mammalian cells by chromate.

Chromate compounds induced sister chromatoid exchanges (SCEs) and chromosome aberrations in cultured mammalian cells. Similar increases in SCE frequency were observed in human fibroblasts exposed to the compounds K2Cr2O7 and K2CrO4. Marked increases in SCE frequency in cells exposed to chromate for a 48-h period were detected at concentrations between 10(-7) and 10(-6) M. Chromosome aberrations (primarily chromatid breaks) were also produced in human cells exposed to K2CrO4 at concentrations between 8 . 10(-7) and 3 . 10(-6) M. K2CrO4, but not the trivalent compound CrCl3, induced SCEs in Chinese hamster ovary (CHO) cells at low concentrations.

Adult↗
PubMed1979

Effects of arginine deprivation upon chromosome aberrations, sces and survival of cho cells treated with mutagenic agents.

Arginine deprivation sensitizes CHO cells to the clastogenic activity of the mutagenic agents UV light, N-methyl-N'-nitro-N-nitrosoguanidine, mitomycin C and 4-nitroquinoline-1-oxide. Cells were allowed to undergo proliferative arrest by deprivation of the amino acid arginine, treated with mutagenic agent and refed with complete medium. The resulting mitotic cells displayed more chromosome aberrations than did mitotic cells in proliferating cell cultures which had been treated similarly. This effect was observed at each dose tested (representing a 300-fold range in concentration). Survival of arginine-deprived cells exposed to UV light was also markedly reduced in comparison to the response of proliferating cells. Sister-chromatid exchange levels induced by MNNG, in contrast, were similar in arginine-deprived and proliferating cells.

4-Nitroquinoline-1-oxide↗
PubMed1979

Induction of sister-chromatid exchanges in Chinese hamster ovary cells by thiol and hydrazine compoudns.

Cysteine, cysteamine and glutathione all induce sister-chromatid exchanges (SCEs) in Chinese hamster ovary (CHO) cells when applied to cell cultures at concentrations between 10(-4) and 10(-2) M. Acute exposure of cells th thiol compound for a period of 2--3 h resulted in a unique dose--response relationship in each instance. This consisted of two peak SCE frequencies, one at either extreme of the concentration range. Each peak corresponded to a 2--3-fold increase over the spontaneous level. A chronic exposure of 24 h, in contrast, resulted in a dose--response relationship consisting of a single peak SCE frequency (representing a 4--5-fold increase over the spontaneous level) at a concentration of approx. 4 x 10(-4) M. The effect of Cu2+ ions included in the medium at a concentration of 10(-5) M was to increase the toxicity and, at some concentrations, the SCE levels occurring after either acute or chronic exposure to thiols. Hydrazine and its derivatives, dimethylhydrazine and isonicotinic acid hydrazide (isoniazid), as well as hydrogen peroxide, also induce SCEs in CHO cells. A 2--3-fold increase over the spontaneous level was observed, depending upon the particular treatment protocol applied. SCE yields after 3 h treatment with dimethylhydrazine and isoniazid were increased if Mn2+, but not Cu2+, was included in the tissue culture medium at a concentration of 10(-5) M. SCE yields after a 24-h treatment with dimethylhydrazine in which Mn2+ was present in, and absent from, the medium were similar. Catalase was observed to reduce the SCE levels resulting from treatment with hydrogen peroxide, dimethylhydrazine and isoniazid. The effect of catalase upon SCEs induced by dimethylhydrazine and isoniazid in the presence of Mn2+ was more evident than when Mn2+ was not included in the culture medium. The significance of these results with respect to the possible active chemical species produced and the mutagenic/carcinogenic risk associated with thiol and hydraizine compounds is discussed.

Animals↗
PubMed1979

Can mutation theories of carcinogenesis set priorities for carcinogen testing programs?

The recent activity in designing, validating and implementing short-term tests for carcinogens has been spurred by the fairly convincing correlation between the carcinogenicity and mutagenicity of chemicals and by the assumption that mutations are somehow involved in neoplastic transformation. Moreover, it has been tacitly assumed that the mutagenic capacity alone of compounds would induce regulatory agencies to pass rules for their removal from man's environment, and would lead the public to avoid them. The actual response, however, is quite different. Government departments shy away from making any decisions on the basis of in vitro test systems, the public at large is becoming irritated by daily announcements that many of their cherished habits could adversely affect their health, and industries feel threatened and may reduce their search for new beneficial chemicals. The reluctance to accept wholeheartedly the mutagenicity tests for the detection of carcinogens is partly due to the uncertainty about the involvement of mutations in the formation of benign and malignant tumors. Following the initial rapid advances in the detection of environmental chemicals with carcinogenic and mutagenic properties, we seem to have arrived at the cross roads: we must now set new priorities for future research, and must make an unbiased assessment of the actual hazard of a compound to man and the human population.

Animals↗
PubMed1979

Enhancement of the chromosome-damaging action of ascorbate by transition metals.

Freshly prepared ascorbate inhibited mitosis and induced chromosome aberrations in cultured Chinese hamster ovary cells. Cu(II) and Mn(II) (10(-4) or 10(-5) M) enhanced both actions. Fe(II) and Fe(III) (10(-4) or 10(-5) M) reduced or abolished the mitosis-inhibiting action of ascorbate. At 10(-4) M, Fe(II) and Fe(III) strongly enhanced the chromosome-damaging capacity of ascorbate. Up to 100% of all examined metaphase plates had multiple chromosome exchanges or breaks. Since the cytostatic and clastogenic effect of ascorbate of H2O2 to induce chromosome aberrations was examined. H2O2 and a H2O2: Fe(II) mixture (Fenton reagent) induced chromosome breaks and exchanges but to a lesser degree than did ascorbate: Cu(II), Mn(II), Fe(II), or Fe(III) mixtures. Whether the strong chromosome damaging capacity of ascorbate plus transition metals as seen in the in vitro test system poses a health hazard only properly designed in vivo studies can reveal.

Animals↗
PubMed1978

The mutagenicity and cytotoxicity of selenite, "activated" selenite and selenate for normal and DNA repair-deficient human fibroblasts.

At doses varying from 8 x 10(-5) to 3 x 10(-3) M sodium selenite (Na2SeO3) induced DNA fragmentation, DNA-repair synthesis, chromosome aberrations and a mitotic inhibition in cultured human fibroblasts. The response of DNA repair-deficient xeroderma pigmentosum (XP) fibroblasts to selenite is comparable to that of control cells. Incubation with mouse liver S-9 microsomal fraction increased the capacity of selenite to induce chromosome aberrations, DNA-repair synthesis and a lethal effect. XP cells behaved as control cells when treated with activated selenite. Sodium selenate (Na2SeO4) at doses ranging from 8 x 10(-5) to 3 x 10(-3) M could not be activated by incubating with a S-9 preparation. Selenate had the capacity to induce a small but significant DNA-repair synthesis.

Adolescent↗
PubMed1978

The use of short-term tests to measure the preventive action of reducing agents on formation and activation of carcinogenic nitroso compounds.

The effect of reducing agents on the nitrosation of methylguanidine (MG) and on the in vitro activation of dimethylnitrosamine (DMN) was examined by measuring DNA-repair synthesis (unscheduled incorporation of [3h]TdR), shifts in alkaline sucrose gradients, frequency of chromosome aberrations, and clone-forming capacity of cultured human fibroblasts. The reducing agents examined were sodium ascorbate, cysteine, cysteamine, and propyl gallate. Since the short-term bioassays used can be quantitated, it has become relatively easy to detect the inhibitory action of reducing compounds on the nitrosation reaction of MG and metabolic activation (with S-9 preparation) of the precarcinogen DMN, to measure their effective dose range, and to establish the most effective ratios between inhibitory agent and reactant. The results indicate that DNA-repair synthesis is a suitable short-term test for studying the numerous combinations and premutations between several carcinogenic or non-carcinogenic agents, and for estimating the capacity of inhibitory agents to affect formation and activation of chemical carcinogens.

Adolescent↗
PubMed1978

The inhibitory effect of cysteine on the mutagenic activities of several carcinogens.

The Salmonella/microsome mutagenesis assay was used to determine the effect of cysteine (alpha-amino-beta-mercaptopropionic acid) on the mutagenic actions of several carcinogens: N-methyl-N'-nitro-N-nitrosoguanidine. N-acetoxy-2-acetylaminofluorene, N-hydroxy-2-acetylaminofluorene, 4-nitroquinoline-1-oxide, methyl methanesulfonate, 5-nitro-2-furaldehyde semicarbazone, 2-(2-furyl)-3-(5-nitro-2-furyl) acrylamide, aflatoxin B1 and the nitrosation products of methylurea and methylguanidine. Cysteine, at non-toxic concentrations, significantly decreased the frequency of reversion to histidine prototrophy when it was added to treatment mixtures. The extent of the inhibition of mutagenic action by cysteine depended on the carcinogen studied as well as the doses of cysteine and carcinogen employed. Cysteine (2.5--10 mM) completely inhibited the mutagenic actions of N-methyl-N'-nitro-N-nitrosoguanidine and methylguanidine nitrosation products while only partially preventing the mutagenic effects of the other carcinogens assayed. Inhibition of 5-nitro-2-furaldehyde semicarbazone-induced mutagenesis occurred only with higher cysteine concentrations (20--200 mM).

2-Acetylaminofluorene↗
PubMed1978

The need for a mammalian test system for mutagens: action of some reducing agents.

Reducing agents and cysteine, cysteamine, glutathione, ascorbic acid and H2O2 with and without the addition of Cu2+ did not increase significantly the frequency of mutations in the Salmonella test at non-toxic concentrations but triggered a marked DNA repair synthesis and induced a relatively high frequency of chromosome aberrations in cultured mammalian cells. Both latter effects were reduced by the addition of catalase to solutions of the reducing agents plus Cu2+. To avoid 'False Negatives' in mutagenicity screening the use of several test subjects including mammalian cells seems to be required.

Animals↗
PubMed1978

Hyperthermia and host-cell reactivation of adenovirus 12.

Exposure of cultured human fibroblasts to hyperthermia delayed the host-cell reactivation of UV-irradiated human adenovirus type 12 (AD12). The experimental design consisted of irradiating human AD12 with UV doses ranging from 180 to 1800 ergs/mm2, infecting human cell populations at 37 degrees C, exposing the infected cells for 7 h to 39.5 degrees C and 41.8 degrees C, returning them to 37 degrees C and estimating the frequency of cells with intranuclear viral inclusion bodies (IB) 41 and 89 h after hyperthermia treatment. Hyperthermia reduced the fractions of fibroblasts with viral IB in the 41 h samples. By 89 h the capacity to form IB in the treated cells was comparable to that in control cells. Hyperthermia of 39.5 and 41.8 degrees C for 7 h did not affect the replication of nonirradiated AD12. The pattern of host-cell reactivation of AD12 following hyperthermia was compared to that in DNA repair deficient xeroderma pigmentosum cell populations.

Adenoviruses, Human↗