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Biomedical subjects

H Marquardt

Publications and source records attributed to H Marquardt.

At least 19 recordsLinked to original sources
PubMed1979

Human fibrosarcoma cells produce fibronectin-releasing peptides.

A sensitive radioimmunoassay, specific for human fibronectin, was used to measure the ability of certain biologically active polypeptides to release fibronectin from cultured human lung fibroblasts into their culture media. Concentrated, serum-free supernatant from a human fibrosarcoma cell line was fractionated by gel filtration chromatography in the presence of acetic acid. Various polypeptides with molecular weights between 46,000 and 6,000 were tested for their ability to release fibronectin from cells. The column fraction, containing polypeptides with an apparent molecular weight of 10,000, exhibited the ability to rapidly release fibronectin from target cells. The activity could be inhibited by phenylmethyl sulphonylfluoride. Several other hormonal factors, tested in parallel with the column fractions, failed to show this effect. The 10,000 dalton molecular weight polypeptides may represent a family of cellular gene products responsible for maintenance of low levels of surface associated fibronectin in fibrosarcoma cells and thus be related to their infiltrating properties by preventing the formation of the extracellular matrix.

Animals↗
PubMed1979

The application of mitotic gene conversion in Saccharomyces cerevisiae in a pattern of four assays, in vitro and in vivo, for mutagenicity testing.

The induction of mitotic gene conversion of the nitrofuran derivatives nitrofurantoin (N-(5-nitro-2-furfuryliden)-1-aminohydantoin), nifurprazinum (1-(5-nitro-2-furyl)-2-(6-amino-3-pyridazyl)-ethylenehydrochloride) and FANFT (2-formylamino-4-(5-nitro-2-furyl)thiazole) was investigated in the D4-RDII strain of Saccharomyces cerevisiae (heteroallelic at the gene loci ade2 and trp5, respiration-deficient). A battery of tests was applied: direct action of the substance to yeasts, the liver microsome test in vitro, the host-mediated assay and the urinary assay. From the various combinations of positive and negative results, additional pharmacokinetic conclusions were drawn. The three nitrofuran derivatives gave positive results by direct action and in the urine of rats. The additon of liver microsomes of mice in the test in vitro reduced the number of induced convertants. In the first hours, a great deal of nitrofurantoin given orally to rats was excreted in the urine, as shown by a high genetic activity. Nifurprazinum and FANFT were excreted to a lesser extent or more slowly. Addition of glucuronidase/arylsulfatase reduced the genetic activity in the urine in the case of nitrofurantoin, had an increasing effect with nifurprazinum and was without any effect in the case of FANFT. In the host-mediated assay, only nitrofurantoin gave positive results. These results seem to be a consequence of the quick but different excretion of the nitrofuran derivatives.

Animals↗
PubMed1979

Comparison of mutagenesis and malignant transformation by dihydrodiols from benz[a]anthracene and 7,12-dimethylbenz[a]anthracene.

Five dihydrodiols derived from benz[a]anthracene (BA) and 4 dihydrodiols derived from 7,12-dimethylbenz[a]anthracene (DMBA) have been tested, together with the parent hydrocarbons, for their abilities to induce mutations to 8-azaguanine resistance in V79 (Chinese hamster cells and malignant transformation in M2 mouse fibroblasts. The syn- and anti-isomers of benz[a]anthracene 8,9-diol 10,11-oxide were also tested for biological activity in these two systems. The non-K-region 1,2- and 3,4-dihydrodiols of BA induced mutations but the non-K-region 8,9-dihydrodiol and the K-region 5,6-dihydrodiol were inactive as mutagens; none of these BA diols transformed M2 mouse fibroblasts. The 3,4- and the 8,9-dihydrodiols derived from 7,12-dimethylbenz[a]anthracene induced mutations in V79 cells and malignant transformation in M2 mouse fibroblasts and both were more active than the hydrocarbon itself. The K-region 5,6-dihydrodiol and the non-K-region 10,11-dihydrodiol of DMBA were inactive in both test systems. The results are not inconsistent with other data suggesting that the metabolic activation of both BA and DMBA occurs through conversion of the respective 3,4-dihydrodiols into the related vicinal diol-epoxides, although other dihydrodiols may also be involved in vivo. Both the BA diol-epoxides tested were mutagenic, but although the anti-isomer transformed M2 fibroblasts, the syn-isomer was inactive.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1978

Effects of benzo(a)pyrene adducts of DNA synthesis in vitro.

Two diol epoxides of benzo(a)pyrene (BP), and benzo(a)pyrene 4,5-oxide, have been used to make adducts in the homopolymers polyribocytidylic acid, (rC); polyriboadenylic acid (rA), polydeoxycytidylic acid (dC) and polydeoxyadenylic acid (dA). With appropriate oligomers as primers these modified and unmodified polynucleotides were used as templates for DNA synthesis with avian myeloblastosis virus DNA polymerase (AMV) or E. coli Pol I DNA polymerase. We have found that: (1) the size of the DNA product is not markedly decreased by the presence of these these polycyclic aromatic hydrocarbon adducts in the templates; (2) the presence of adducts does not lead to increased incorporation of erroneous bases. These results, supported by kinetic data, suggest that these polymerases can bypass a site containing an adduct on the template without leaving a gap or causing misincorporation of a base and they imply that mutagenesis by BP may not be attributable to either of these mechanisms.

Avian Myeloblastosis Virus↗
PubMed1977

The metabolic activation of 7-methylbenz(a)anthracene: the induction of malignant transformation and mutation in mammalian cells by non-K-region dihydrodiols.

Four different dihydrodiols derived from 7-methylbenz(a)anthracene have been tested, together with the parent hydrocarbon, for their ability to induce the in vitro malignant transformation of mouse M2 fibroblasts and mutations in V79 Chinese hamster cells. In the transformation tests withe the non-K-region dihydrodiols, the 3,4-diol was the most active dihydrodiol tested and the 8,9-diol was also more active than 7-methylbenz(a)anthracene itself; the 1,2-diol showed only slight activity. The K-region dihydrodiol, the 5,6-diol, which cannot be directly metabolized to a vicinal diol-epoxide, was inactive. These differences in biological activity were similar to those apparent in the results from the mutagenicity tests. The data support the general hypothesis that non-I-region dihydrodiols, which can be metabolized to vicinal diol-epoxides, are important in the metabolic activation of the carcinogenic polycyclic hydrocarbons and, when taken together with other results, indicate that 3,4-dihydro-3,4-dihydroxy-7-methylbenz(a)anthracene is most probably involved in the metabolic activation of 7-methylbenz(a)anthracene presumably following conversion into the related diol-epoxide, 3,4-dihydro-3,4-dihydroxy-7-methylbenz(a)anthracene 1,2,-oxide.

Animals↗
PubMed1977

Mutagenic activity of nitrite-treated foods: human stomach cancer may be related to dietary factors.

By the Salmonella typhimurium test, extracts of Japanese raw fish treated in the laboratory with nitrite showed mutagenic activity which is prevented by addition of ascorbate. Extracts from similarly treated beef and hot dogs were nonmutagenic. The data conform to a working concept that the high stomach cancer incidence in Japanese and certain other populations may be due to specific dietary factors of an alkylnitrosamide type.

Animals↗
PubMed1977

Envelope glycoproteins of Rauscher murine leukemia virus: isolation and chemical characterization.

The envelope glycoproteins (designated gp70 and gp45) of the Rauscher strain of murine leukemia virus were solubilized by osmotic shock and freeze-thawing in chaotropic solutions. The viral glycoproteins were then purified by phosphocellulose chromatography and gel permeation chromatography on Bio-Gel A-1.5m. Yields by this procedure were 6.2% for gp70 and 1.3% for gp45 on a protein input basis. The apparent molecular weights were respectively 67 500 and 47 500 with a polypeptide chain molecular weight of approximately 45 000 for both glycoproteins. Amino acid analysis showed a high degree of similarity for both components, with some differences subject to further evaluation. The total carbohydrate content was approximately 32% for gp70 and 6-9% for gp45. In keeping with the amino acid compositional similarity suggesting relationships, alanine was found to ba the amino-terminal amino acid of both glycoproteins, and cross-reactivity was demonstrated by immunologic tests. The data suggest that the chief difference between gp70 and gp45 lies in the carbohydrate content.

Amino Acids↗
PubMed1977

Urolithiasis in childhood.

The management of 131 children with urinary calculi is described. Boys out-numbered girls 2:1. Five per cent of the patients had identifiable metabolic causes, while 78 per cent had infected renal lithiasis. With appropriate therapy, stone disease became inactive in 79 per cent of the children. The remaining 21 per cent continued with active disease. Stone formation may be regarded as a solitary complication or one of several manifestations of a large number of underlying disorders. Along with a thorough search for etiologic factors there must be an equally aggressive therapeutic effort. Becuase the disease is often sporadic, careful long-term follow-up of the patients with active as well as those with inactive stone disease is mandatory.

Age Factors↗
PubMed1977

Malignant transformation and mutagenesis in mammalian cells induced by vicinal diol-epoxides derived from benzo(a)pyrene.

Benzo[a] pyrene and the syn- and anti-isomers of the 7,8-diol 9,10-oxide and of the 9,10-diol 7,8-oxide derived from this hydrocarbon have been tested for their abilities to induce malignant transformation in M2 mouse fibroblasts and mutagenesis in V79 Chinese hamster cells. The anti-isomer of the 7,8-diol 9,10-oxide induced more mutations and transformation than did the other three vicinal diol-epoxides. The two 9,10-diol 7,8-oxides were moderately mutagenic but did not induce any transformation. In contrast, benzo[a]-pyrene induced transformation in M2 fibroblasts but was not mutagenic in the V79 cells.

Animals↗
PubMed1977

Microsomal metabolism of chemical carcinogens in animals and man.

As the first step in the interaction between chemical carcinogen and cell, it has been recognized that most carcinogens, being chemically inert, must be metabolically converted into reactive, electrophilic 'ultimate carcinogens'. Ironically, the enzymes that activate carcinogens are the same microsomal, drug-metabolizing enzymes, mostly mixed-function oxidases, whose primary function is the detoxification and disposal of foreign chemicals. From the limited data available, it appears that, qualitatively, animals and man metabolize carcinogens via very similar pathways. However, in animals as well as in man there are marked species-related and individual differences in the basal levels of microsomal metabolism as well as in its inducibility. Therefore, the extrapolation to man of existing animal data on metabolic activation and carcinogenesis of chemicals is at present impossible. However, it might be possible to detect 'high-risk' individuals, i.e., individuals who might be especially endangered by exposure to environmental carcinogens due to their high rate of metabolism (for instance, some cigarette smokers), by determinations of human microsomal metabolism in vitro, using human leucocytes, or in vivo, employing safe drugs which are metabolized in a similar way to carcinogens, as indirect indices for individual variations in microsomal metabolism.

Animals↗
PubMed1976

Late results following cryosurgery of the prostate in 111 high-risk patients.

The so-called cryoprostatectomy was performed on 111 high-risk patients from November 1970 to December 1975 (60-month period). 86 patients (78.5%) had an adenoma and 25 patients (21.5%) a carcinoma of the prostate. During this period of time 1,085 more patients with adenoma or carcinoma were treated by open prostatectomy or TUR. Experience has shown that cryoprostatectomy should be performed only on high-risk patients whose physical condition excludes operation and the only alternative would be continuous urethral catheter drainage. Any further indication must be rejected.

Aged↗
PubMed1976

Tumorigenicity in vivo and induction of malignant transformation and mutagenesis in cell cultures by adriamycin and daunomycin.

The two anthracycline antitumor antibiotics, adriamycin and daunomycin, have been tested for tumorigenic activity, and the results confirm previous findings that they can induce mammary tumors in female rats receiving single i.v. doses. Both substances are highly potent in producing malignant transformation and mutation in mammalian cell systems in vitro. Their transformming activity is comparable to that of the potent carcinogen, N-methyl-N'-nitro-N-nitro-soguanidine. Actinomycin D, although similar to the anthracyclines in having high binding affinity for DNA, is only minimally effective in the same in vitro systems and its direct carcinogenic activity in vivo is moot. These results suggest that satisfactory correlations may be obtainable between tests for tumorigenicity in vivo, and assays for transformation and mutagenesis in vitro, and that adriamycin, and daunomycin may have carcinogenic potential in man.

Adenocarcinoma↗