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Biomedical subjects

H F Stich

Publications and source records attributed to H F Stich.

At least 109 records · Page 6Linked to original sources
PubMed1978

Inhibitory effect of reducing agents on N-acetoxy- and N-hydroxy-2-acetylaminofluorene-induced mutagenesis.

The effect of cysteine (alpha-amino-beta-mercaptopropionic acid) on the mutagenic activities of the proximate carcinogen, N-hydroxy-2-acetylaminofluorene, and the ultimate carcinogen, N-acetoxy-2-acetylaminofluorene, was examined by estimating the frequency of his+ revertants of Salmonella typhimurium. Nontoxic concentrations of cysteine significantly reduced the formation of revertants when it was applied concurrently with the two carcinogens. Cysteine showed no detectable effect on mutagenesis when added to bacteria before or after exposure to carcinogens. The magnitude of inhibition of mutagenesis depended on the dose of cysteine and the concentration of the carcinogens. Cysteine at equimolar concentrations inhibited to a larger degree the mutagenesis induced by N-hydroxy-2-acetylaminofluorene than it inhibited that elicited by N-acetoxy-2-acetylaminofluorene. The inhibitory action of cysteamine and glutathione was comparable to that of cysteine. The results appear to be consistent with the assumption that cysteine traps electrophiles prior to their action on DNA.

Acetoxyacetylaminofluorene↗
PubMed1977

Geographic variations in tumor prevalence among marine fish populations.

A global epidemiological study on the frequency of skin papillomas among various flatfish species (Pleuronectids), papillomas of eels and the virus induced lymphocystis disease has revealed particular distribution patterns. Skin papillomas are prevalent among at least 20 flatfish species of the northern Pacific Ocean, Bering Sea, Sea of Okhotsk, and Japan Sea but appear to be absent from the Atlantic, North Sea, and the Caribbean Sea. The opposite is found for lymphocystis, which is common among flatfish species of the Atlantic shores of Europe and North America. Similarly the skin papillomas of eels are restricted to relatively small region along the European coast extending from the Baltic countries to Denmark, Germany and Holland. Superimposed on this global distribution pattern are local variations in tumor prevalences which can vary from about 58% to 0.01%. The geographic distribution pattern points to the existence of areas around the globe in which flatfish or eels are able to develop skin papillomas. Outside these areas of "potential skin papilloma risk," flatfish and eel populations are not afflicted with papillomas even if they inhabit estuaries or rivers with a high man-made or naturally-occurring pollution.

Animals↗
PubMed1977

Differential sensitivity of Xeroderma pigmentosum cells of different repair capacities towards the chromosome breaking action of carcinogens and mutagens.

The sensitivity of cultured fibroblasts obtained from four unrelated Xeroderma pigmentosum patients (XP-K, XP-C, XP-E and XP-H), which showed different DNA repair levels, was examined. The frequency of metaphase plates with chromosome aberrations and the frequency of breaks and exchanges per chromosome complement were estimated following exposure to the carcinogens 4-nitroquinoline-1-oxide (4NQO),N-acetoxy-2-acetyl-aminofluorene (N-acetoxy-2-AAF), and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), and to the mutagen daunomycin. The frequency of chromosome aberrations (breaks and exchanges) increased in the order (XP-K less than XP-C less than XP-E less than XP-H) with decreasing DNA repair capacity of the XP cells examined (XP-K greater than XP-C greater than XP-E greater than XP-H) following 4NQO and N-acetoxy-2-AAF. MNNG induced DNA repair synthesis and chromosome aberrations in the four XP cell types at levels comparable to those in fibroblasts of non-afflicted persons. Daunomycin triggered no DNA repair synthesis but induced similar frequencies of chromosome aberrations in the XP cells and controls. Heterozygous XP cells from parents of XP-K, XP-E and XP-C responded as control cells towards the three carcinogens and the mutagen used. Xeroderma pigmentosum can be considered to be an "induced" chromosome instability syndrome, in contrast to Bloom's syndrome or Fanconi's anaemia, which are "spontaneous" chromosome breakage syndromes according to German's definition.

4-Nitroquinoline-1-oxide↗
PubMed1977

Comparative electrophilicity, mutagenicity, DNA repair induction activity, and carcinogenicity of some N- and O-acyl derivatives of N-hydroxy-2-aminoflourene.

N-Myristoyloxy-N-acetyl-2-aminofluorene, N-acetoxy-N-myristoyl-2-aminofluorene, N-myristoyloxy-N-myristoyl-2-aminofluorene, and N-hydroxy-N-myristoyl-2-aminofluorene each yielded a high incidence of sarcomas in male rats within 5 to 7 months after s.c. injection of 64 micronmoles in divided doses. N-Acetoxy-N-acetyl-2-aminofluorene and N-hydroxy-2-acetylaminofluorene, although potent carcinogens at the s.c. site, were less active than the above derivatives with a myristoyl substituent. N-Sulfonoxy-N-acety--2-aminofluorene (purity larger than or equal to 70%) had little or no carcinogenic activity when administered in large amounts by s.c. injection to rats. The low incidence of tumors could have resulted from N-hydroxy-2-acetylaminofluorene or other decompostion products of the N-sulfonozy derivative. Each of the N-acetoxy and N-myristoyloxy derivatives of N-acetyl-2-aminofluorene and of N-myristoyl-2-aminofluorene showed electrophilic activity toward methionine; N-acetoxy-N-acetyl-2-aminofluorene was the most reactive and N-myristoyloxy-N-myristoyl-2-aminofluorine was the least reactive. Each of these esters also induced unscheduled tritiated thymidine incorportation in nondividing cultured human fibroblasts and thus appeared to induce lesions in DNA that lead to repair synthesis. EACH OF THE N-acetoxy derivatives was highly mutagenic for Salmonella typhimurium strains TA98 and TA1538 without tissue activation; neither N-myristoyloxy derivative was mutagenic under these conditions. While there was a qualitative correspondence between several of the above activities of these 2-aminofluorene derivatives, the quantitative differences and the lack of detectable mutagenicity of the 2N-myristoyloxy derivatives for S. typhimurium indicate the need for multiple short-term tests in the qualitative prediction of potential carcinogenic activity.

Animals↗
PubMed1977

Possible use of short-term tests for carcinogens in experimental epidemiology.

This brief overview pointed out the feasibility of applying the recently developed short-term bioassays for carcinogens/mutagens to the field of epidemiology. The simplicity and economy of these test systems permitted their adaptation for large-scale screening for intrinsic and extrinsic carcinogens with an eye to detecting subpopulations with elevated sensitivity to particular carcinogens.

Animals↗
PubMed1976

Carcinogens in estuaries, their monitoring and possible hazard to man.

Bottom-dwelling flatfish and their skin tumors can be used as an early-warning-system for the pollution by chemical carcinogens in sub- and inter-tidal waters. A trial in British Columbia and the State of Washington showed a link between tumor prevalence and urban activity. The possible use of marine accumulator organisms (mussels) in the estimation of benzo(a)pyrene levels of harbours is considered. The combination of biological and chemical assays could provide the basis for a large-scale routine surveillance of the marine environment.

Age Factors↗
PubMed1975

The response of Xeroderma pigmentosum cells and controls to the activated mycotoxins, aflatoxins and sterigmatocystin.

The activation of the mycotoxins aflatoxin B1, G1, B2, G2, aflatoxicol and sterigmatocystin by 9S fraction, microsomal preparation (105,000 times g) and supernatant (105,000 times g) of livers of several species was examined. DNA repair synthesis, chromosome aberrations and clone forming capacity were used as endpoints. Cultured fibroblasts of normal persons and DNA repair deficient Xeroderma pigmentosum patients were employed as test subjects. The activation mixtures significantly increase the chromosome breaking function, lethality and DNA damaging effect (measured as DNA repair synthesis) of aflatoxin B1, G1, aflatoxicol ans sterigmatocystin. The DNA repair-deficient XP cells respond to the activated mycotoxins with a low level of unscheduled 3HTdR incorporation as compared to that of control cells, but show a highly elevated sensitivity to the chromosome-damaging and lethal effect of aflatoxin B1 and sterigmatocystin.

Aflatoxins↗
PubMed1975

DNA repair synthesis of cultured human cells as a rapid bioassay for chemical carcinogens.

The feasibility of detection of carcinogenic chemicals using DNA repair synthesis of cultured human fibroblasts as measured by an unscheduled 3HTdR incorporation has been explored. Of 64 chemicals tested, 29 were proximate or ultimate carcinogens, 15 were precarcinogens that required metabolic activation, 16 were non-oncogenic compounds and 4 were of unknown carcinogenicity. All directly acting carcinogens triggered a DNA repair synthesis, whereas no unscheduled 3HTdR incorporation was observed following the application of the 16 non-oncogenic compounds. As a rule, the precarcinogens (without metabolic activation) do not elicit DNA repair synthesis. However, longer exposures and higher concentrations of the precarcinogens 2-AAF, aflatoxin B1 and sterigmatocystin gave unscheduled 3HTdR uptake. The results suggest the suitability of using repair synthesis as endpoint, and cultured human cells as subjects in a prescreening programme for chemical carcinogens.

Adolescent↗
PubMed1975

Response of homozygous and heterozygous xeroderma pigmentosum cells to several chemical and viral carcinogens.

The topics discussed include the relationship between the carcinogenic property of various compounds and their capacity to elicit DNA damage that results in a DNA repair synthesis; the metabolic activation of precarcinogens; the in vivo use of DNA repair synthesis in the identification of tissues that will give rise to neoplasms; the possible involvement of DNA repair in the sensitivity of human cells to the chromosome-damaging and lethal effect of chemical carcinogens; the different responses of homozygous xeroderma pigmentosum (XP) cells, heterozygous XP cells, and controls to some but not all chemical carcinogens and oncogenic viruses; and the possible link between DNA damage, its repair, and viral-induced neoplastic transformation.

Carcinogens↗
PubMed1975

Reduced DNA repair capacity and increased cytotoxicity following split doses of the mutagen 4-nitroquinoline-1-oxide in cultured human cells.

Cultured human fibroblasts were exposed to single doses of 4-nitroquinoline-1-oxide(4NQO) and to two equimolar doses of 4NQO at intervals varying from 0.5 to 12 h. DNA repair synthesis as measured by an unscheduled uptake of tritium-labelled thymidine ([3-H]TdR), cell survival as estimated by the clone-forming capacity, and frequency of chromosome aberrations were used as endpoints. Cells respond with a reduced level of DNA repair synthesis when the second 4NQO dose (5 X 10 minus 7 or 1 X10-minus 7 M) is given within 3 h of the first 4NQO dose. If the interval between the two doses is 5 h or more, the level of DNA repair synthesis which is induced by the second 4NQO dose is comparable to that following a single 60-min 4NQO application. In this 3-h period the cultured cells show an increased sensitivity to the lethal effect and chromosome-damaging action of the second 4NQO dose. The reduced period of DNA repair capacity seems to increase the mutagenic effect of the chemical carcinogen.

4-Nitroquinoline-1-oxide↗
PubMed1975

The search for relevant short term bioassays for chemical carcinogens: the tribulation of a modern Sisyphus.

Based on a good correlation between carcinogenicity and mutagenic activity several rapid microbial bioassays for chemical carcinogens have been recently developed. We would like to suggest, that these microbial tests should be followed by bioassays using cultured human cells of the "average" man, and of persons with elevated cancer risk or increased susceptibility to carcinogenic agents. The main objective of using DNA repair (unscheduled uptake of 3HTdR) and DNA fragmentation (shift in sedimentation profiles) of cultured human cells was to design a test system that can simulate conditions found in man and thus provide information relevant to the human population. A trial on 98 different carcinogens, precarcinogens and noncarcinogens showed the suitability of DNA repair synthesis as a rapid, economic and relevant assay for detection of chemical carcinogens. To check the adaptability of DNA repair synthesis of human cells as a bioassay for chemical carcinogens we examined carcinogenic nitrosation products which are formed from the interaction of nitrite and nitrosatable compounds, carcinogenic or mutagenic photosensitizing chemicals, and the effect of complex interactions. Organotropic carcinogens can be detected by measuring DNA fragmentation and DNA repair in various target organs following the in vivo application of chemical carcinogens. The pros and cons of several bioassays and their usefulness in judging a carcinogenic or mutagenic hazard to human populations is discussed.

Animals↗