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Biomedical subjects

E Eder

Publications and source records attributed to E Eder.

At least 73 records · Page 4Linked to original sources
PubMed1984

Carcinogenicity study of trichloroethylene, with and without epoxide stabilizers, in mice.

Previous analytical studies of industrial samples of trichloroethylene (TRI) have revealed the presence of mutagenic and carcinogenic epoxides which, it was proposed, might be responsible for the carcinogenicity of such samples, as demonstrated with mice in other laboratories. To test this hypothesis, Swiss mice (ICR/HA) of both sexes, bred and kept in SPF conditions, were dosed daily with TRI in corn oil by gavage (males: 2.4 g/kg, females: 1.8 g/kg) with or without the addition of epichlorohydrin (EPC, 0.8%, w/w), 1,2-epoxybutane (BO, 0,8%), or EPC + BO (0.25% + 0,25%) for 18 months. The ensuing observation period terminated at 106 weeks (from start of experiment). Gross and microscopic examination of all organs revealed a statistically significant increase in the incidence of forestomach papillomas and carcinomas after EPC-, BO-, and (EPC + BO)-stabilized samples of TRI, but not after pure, amine base-stabilized TRI. This type of tumor is believed to be induced by the direct alkylating epoxides epichlorohydrin and epoxybutane, whose industrial use in stabilizing chlorinated aliphatic hydrocarbons should be discontinued. No other significant increase in tumor incidences was found. Again, this study does not support the suggestion that trichloroethylene itself is carcinogenic under realistic exposure conditions.

Animals↗
PubMed1983

A new pathway of acrolein metabolism in rats.

The excretion of metabolites of acrolein in rat urine after single oral administration of 10 mg/kg was investigated. S-Carboxyethylmercapturic acid (S-carboxyethyl-N-acetyl-cysteine), or S-(propionic acid methyl ester)mercapturic acid, was found as the major metabolite. An unidentified metabolite was found in expired air. Acrylic acid and methyl acrylate are suggested as intermediates in the metabolism of acrolein.

Acrolein↗
PubMed1983

Induction of unscheduled DNA synthesis in HeLa cells by allylic compounds.

Thirteen allylic compounds, mostly with close structural relationship, were tested for their ability to induce unscheduled DNA synthesis (UDS) in HeLa cells and mutations in the Ames test; 11 induced UDS in dose dependence. Allyl isothiocyanate was negative in UDS (borderline in the Ames test) and acrolein (positive in the Ames test) proved toxic to HeLa cells, therefore UDS measurement was excluded. In general, positive qualitative and quantitative correlation between UDS, Ames test and alkylating properties (as measured in the 4-nitrobenzyl-pyridine test, NBP) were found. Among structural analogs and typical allylic compounds with various leaving groups, the amount of induced DNA repair at equimolar concentrations decreased in the same order as the mutagenic and alkylating activities in the other 2 test systems: 1,3-dichloropropene (cis) greater than 1,3-dichloropropene (trans) greater than 2,3-dichloro-1-propene; 1-chloro-2-butene greater than 3-chloro-1-butene greater than 3-chloro-2-methyl-1-propene greater than allyl chloride; allyl-methane-sulfonate greater than -iodide greater than -bromide greater than -chloride.

Allyl Compounds↗
PubMed1982

Correlation of alkylating and mutagenic activities of allyl and allylic compounds: standard alkylation test vs. kinetic investigation.

Thirty-nine allylic and non-allylic compounds have been tested in the standard 4-(p-nitrobenzyl)pyridine (NBP) alkylating procedure and the Salmonella typhimurium mutagenicity assay. Fourteen of these were found directly mutagenic (without addition of S-9 mix activating enzyme system). With twelve of these compounds, a good correlation of alkylating and mutagenic potencies was established; the remaining two do not meet the chemical conditions of the NBP procedure on account of HCl elimination with these two compounds. The other 25 substances were inactive in both systems. The quantitative correlation proved to be almost linear in the lower activity ranges (E approximately 2; revertants/muml approximately 600). The reasons for some deviations from the linear relationship have been analyzed and discussed on the basis of structural features. In addition to the standard alkylation test, a modified NBP-test was performed in order to obtain kinetic data and activation energy values. The results with 6 representative allylic compounds show that the overall correlation is not substantially improved above that of the standard procedure: nonetheless, additional information on reaction characteristics is obtained with some substances.

Alkylating Agents↗
PubMed1982

Mutagenic properties of allylic and alpha, beta-unsaturated compounds: consideration of alkylating mechanisms.

1. Allyl and allylic compounds may exert alkylating activities by SN1, SN2 and SN2' mechanisms. This direct alkylating potential can be determined quantitatively by a modified 4-NBP (4-nitrobenzyl pyridine) test. 2. The alkylating activities in a systematically selected series of allyl and allylic compounds correlate well with the direct mutagenic potential as determined in the Ames test using Salmonella typhimurium TA 100 as tester strain. 3. The allylic structure is a prerequisite for these types of activities since structurally related molecules lacking the allylic moiety are inactive in this respect. 4. The potency of both the alkylating and mutagenic activity is determined by the strength of the leaving group: --OSO2CH3 greater than I greater than Br greater than Cl greater than--NCS. 5. Indirect mutagenicity, through metabolic activation of the olefinic bond (by addition of S9 mix to the tester medium), can be ruled out for practically all compounds, the only exception found being 2,3-dichloro-1-propene where an increase of mutagenicity is encountered after addition of S9 mix; mechanistic explanations for this exception are provided. 6. Analogous activation is demonstrated for benzyl halides, the alkylating potency of which is even higher than that of genuine allylic compounds. 7. A variety of methyl- and chlorine-substituted allyl compounds has been included in the study: both groups increase activity, either by +I (CH3) or by +M effects (Cl). 8. alpha, beta-Unsaturated carbonyl compounds, e.g. acrolein and crotonaldehyde, also display direct mutagenic activity which is due to a completely different mechanism: covalent binding to nucleophilic sites of DNA bases by Michael addition. Methyl and other alkyl substitutions decrease the mutagenic potential in this type of compound. The corresponding alcohols, also displaying mutagenic activity but to a lesser degree, are metabolically activated by ADH (alcohol dehydrogenase) of the tester strain microbes to the aldehydes or ketones.

Alkylating Agents↗
PubMed1981

The saphenous neurovascular free flap.

A new neurovascular free-flap donor area on the medial side of the knee is described. The flap is supplied by the saphenous artery, a branch of the descending genicular artery. It is drained both by the long saphenous vein and by the saphenous venae comitantes. Its nerve supply is from the medial femoral cutaneous nerve above the knee and the saphenous nerve below the knee. The flap is thin, has a long vascular pedicle (up to 15 cm) and a dependable nerve supply, and can be made quite large. The principal disadvantage is the donor wound, which requires grafting in most cases. We describe the anatomy of the saphenous flap, the method of raising it, and our early clinical experience with it both as a free flap and as a pedicled flap. Potential uses of the saphenous flap and its broader significance in relation to flaps on the lower extremity are briefly discussed.

Adolescent↗
PubMed1980

Carcinogenicity study of trichloroethylene by longterm inhalation in three animal species.

Pure trichloroethylene (tri), stabilized by an amine base, was administered by inhalation at 0, 100, and 500 ppm for 6 h/day, 5 days/week, for 18 months to mice, rats and Syrian hamsters of both sexes. No significant increase in tumor formation was observed in any species or dosing group, except in malignant lymphomas, which were increased in female mice in the following incidence rates: 9/29 (controls), 17/30 (100 ppm), and 18/28 (500 ppm). Whether or not this high occurrence of lymphomas, which is peculiar to this strain of mice (NMRI) has any relationship to tri-exposure, cannot be decided upon by the present experiment. It is concluded that from these findings no indication for a carcinogenic potential of pure trichloroethylene can be deduced.

Animals↗
PubMed1978

[Stimulation of prolactin secretion by drugs].

Intravenous administration of metaclopramide and cimetidine provokes an immediate rise in serum prolactin concentration. The results are compared with the response of serum prolactin to arginine, insulin and TRH.

Animals↗
PubMed1977

Carcinogenicity of trichloroethylene: fact or artifact?

Technical trichloroethylene has been found carcinogenic in mice after high daily doses per os. A GC-MS analysis of this technical sample revealed the presence of considerable amounts of epichlorohydrin and 1.2-epoxibutane as stabilizers. These epoxides are highly mutagenic in the Ames test and are, most probably, responsible for the carcinogenic effect found in mice. The question whether trichloroethylene is carcinogenic or not remains open.

Carcinogens↗
PubMed1977

The significance of cytotoxicity of lymphocyte populations in coloncarcinoma patients in comparison to normal controls using a new statistical method of evaluation.

Lymphocytotoxicity was studied in patients suffering from colon carcinoma. 125Iododeoxyuridin-labeled established colon carcinoma cells were used as target cells in a cytotoxicity assay according to COHEN et al. (1). They were incubated with unfractionated lymphocytes of the peripheral blood, purified T cells or adherent cells as effector cells. The cytotoxic effect was measured in cpm, i. e. the radioactivity released from the target cells into the supernatant. The cpm were adjusted by eliminating the variables of spontaneous release and for maximal incorporated radioactivity of the target cells. The cytotoxic activity of lymphocytes to colon carcinoma target cells was dose-dependent. It was demonstrated for lymphocytes from colon carcinoma patients as well as for lymphocytes from healthy controls. Although adjusted cpm values were used for statistical analysis lymphocytes from the 20 colon carcinoma patients did not show a higher cytotoxic effect than lymphocytes from the 20 healthy controls. However, when the results were compared separately for each experiment consisting of 2 colon carcinoma patients and 3 healthy controls, statistical significant specific lymphocytotoxicity was demonstrated for lymphocytes from colon carcinoma patients. The plot diagram of the results and the statistical evaluation by the multivariate analysis of variance (Manova) offer a clear and comprehensible representation of the results. Particularly for statistical reasons, this representation is superior to the usual calculation of percent specific lysis. It was demonstrated in this study that the cytotoxic activity in the absence of autologous serum is a function of T cells of the peripheral blood. Adherent cells have a high cytotoxic activity regardless whether the cells were obtained from colon carcinoma patients or from healthy controls.

Adenocarcinoma↗
PubMed1976

Lymphocytotoxicity to tumor target cells and interference of serum factors or tumor antigen with lymphocytotoxicity in patients suffering from different stages of breast carcinoma.

The in vitro cytotoxicity of lymphocytes from patients suffering from breast carcinoma against autochthonous, allogeneic and established breast carcinoma cells was evaluated. Lymphocytotoxicity to breast carcinoma cells was observed in all stages of the disease. Control lymphocytes from healthy donors or patients suffering from other carcinoma are not cytotoxic for the breast carcinoma cell lines. A follow-up study of the cell mediated immune reactions before and after surgical removal of the breast carcinoma showed that the cytotoxic lymphocyte population which is demonstrated in the presence of the tumor disappears quickly after excision of the carcinoma. The non-reactivity of lymphocytes is not due to a general immune defect. Serum of the tumor bearers did not block the lymphocytotoxicity in early stage breast carcinoma; in metastatic disease inhibition occurred in more than half of the cases. Preincubation of lymphocytes with antigen preparations of allogeneic breast carcinoma cells did not inhibit the cytotoxicity to breast carcinoma cells whereas autologous serum preincubated with the antigen preparation diminished the lymphocyte reactivity to the target cells in some cases.

Adult↗
PubMedDate not supplied

Mutagenic and carcinogenic risk of oxygen containing chlorinated C-3 hydrocarbons: putative secondary products of C-3 chlorohydrocarbons and chlorination of water.

Oxygen containing C-3 chlorohydrocarbons are secondary products of C-3 chlorohydrocarbons formed during oxidation at air, in the metabolism of pesticides and by chlorination of drinking water. These compounds are mutagenic, genotoxic and carcinogenic. 2-Chloroacroleins are extremely strong mutagens and genotoxins and form 1,N2-cyclic deoxyguanosine adducts. The role of such adducts in mutagenicity and carcinogenicity is discussed.

Animals↗
PubMedDate not supplied

Genotoxicity of allyl compounds--a quick screening strategy based on structure-activity relationships and a battery of prescreening tests.

A proposed strategy for the rapid screening of the genotoxic activities of allylic compounds is based on structure-activity relationships elaborated by a battery of quick screening tests. The procedure facilitates the selection of appropriate representatives of this class of compound for subsequent testing, so that both expensive and time-consuming assays and the use of animals can be drastically reduced. The studies have yielded several important results. Allylic compounds with suitable leaving groups have been shown to exert direct genotoxic activity. In the metabolic activation of these compounds the formation of epoxides is clearly of minor importance, playing a role only in the case of 2,3-dichloro-1-propene and some of its homologues, whereas all reactive allylic compounds can be activated to genotoxic alpha,beta-unsaturated carbonyl compounds (acrolein). The most significant factors for genotoxicity are the leaving groups and halogen substituents. Alkyl substituents increase the direct genotoxicity while decreasing the indirect activity (via acroleins).

Allyl Compounds↗