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Biomedical subjects

E Dybing

Publications and source records attributed to E Dybing.

At least 127 records · Page 7Linked to original sources
PubMed1980

Developmental aspects of 2-acetamidofluorene metabolism and mutagenic activation in the chick.

1. Oxidative metabolism and mutagenic activation of 2-acetamidofluorene (AAF) in the Salmonella test system were studied with liver subfractions from untreated and beta-naphthoflavone (BNF)-pretreated chicks during the first 10 days after hatching. 2. Newly hatched chicks had high liver microsomal mono-oxygenase activities, and these were markedly increased by BNF-pretreatment. 3. The mutagenic activation of AAF with control liver subfractions was highest on day 1 after hatching and declined towards day 10. 4. BNF-pretreatment caused decreases in the mutagenicity of AAF at high protein concentrations in the test system, but led to increases in mutagenic activity when low protein concentrations were applied. 5. N-Hydroxy-2-acetylaminofluorene was activated to a mutagen by microsomal metabolism, and this reaction was blocked by the deacetylase inhibitor paraoxon. 6. SDS polyacrylamide gel electrophoresis of liver microsomes from BNF-pretreated chicks showed an increase in a band with mol. wt. of approx. 55,000. The increase in the 55,000 mol. wt. band following BNF-pretreatment was associated with increases in benzo[a]pyrene hydroxylase and AAF N-hydroxylase activities in the chick liver microsomes.

2-Acetylaminofluorene↗
PubMed1980

Mutagenicity studies with urine concentrates from coke plant workers.

Urine from coke plant workers, collected before and after work, were tested for the content of mutagenic substances in the Salmonella test system. Urine extracts from exposed smokers showed mutagenic activity, whereas urine from exposed nonsmokers did not. The mutagenicity of exposed smoker's urine was not significantly different from that of urine from nonexposed smokers. Mutagenicity of smokers' urine was only evident in the presence of a rat liver metabolic activation system. The addition of beta-glucuronidase did not enhance the mutagenic effect. The facts that coke plant workers are exposed to very high levels of polycyclic aromatic hydrocarbons (PAH) and that there is no observed enhanced mutagenicity of their urine indicate that the mutagenicity observed with urine from smokers is not due to conventional PAH.

Coal↗
PubMed1980

Hepatic microsomal drug metabolism, glutamyl transferase activity and in vivo antipyrine half-life in rats chronically fed an ethanol diet, a control diet and a chow diet.

The effects of chronic consumption of ethanol on several hepatic enzyme activities were investigated. Male Wistar rats (180 g) were divided in three groups, two of which were pair-fed ethanol or control liquid diets while the third group received chow and water ad libitum (untreated group). The following changes were observed after 1 and/or 6 weeks when expressed per 100 g b.w.: In the ethanol group, the amount of cytochrome P-450 increased as did the activities of aniline hydroxylase and glutamyl transferase. The in vivo half-life of antipyrine decreased. The activity of NADPH cytochrome c reductase in the ethanol group was different from the reference groups, but not changed compared to pre-experimental values. The activities of ethylmorphine N-demethylase and aryl hydrocarbon hydroxylase were decreased when expressed per gram of microsomal protein. In the control group, the activity of NADPH cytochrome c reductase declined and so did hepatic weight. The study gave support to a suspicion that feeding control diet may influence hepatic enzyme activities as well as relative liver weight. This influence may magnify ethanol effects on NADPH cytochrome c reducdase and relative liver weight when such effects are measured as the difference between the control and the ethanol group at single points of time. In addition, our study showed that ethanol should not be regarded as a general inducer of microsomal enzymes.

Alcoholism↗
PubMed1980

Developmental pattern of 3-methylcholanthrene-inducible mutagenic activation of N-2-fluorenylacetamide, 2-fluorenamine, and 2,4-diaminoanisole in the rabbit.

The effects of 3-methylcholanthrene (MCA) on mutagenic activation of the carcinogenic arylamines N-2-fluorenylacetamide (FAA), 2-fluorenamine (FA), and 2,4-diaminoanisole (2,4-DAA) by liver homogenates were studied postnatally in Dutch rabbits. These effects were compared with the developmental profiles of cytochrome P448 and aryl hydrocarbon hydroxylase (AHH) activity. Mutagenic activation of FA and 2,4-DAA was increased by MCA as early as 2 days after birth, whereas induction of FAA mutagenicity appeared 6 days after birth. Thereafter, induction of all three arylamines closely paralleled induction of cytochrome P448, which was maintained into adulthood. In contrast, induction of AHH activity by MCA was highest at 2 days of age and decreased to control levels 20 days after birth.

2-Acetylaminofluorene↗
PubMed1979

Mutagenicity and irreversible binding of the hepatocarcinogen, 2,4-diaminotoluene.

Mutagenicity of 2,4-diaminotoluene (DAT) in the Salmonella mutagenicity assay was increased with liver fractions from phenobarbital (PB) or beta-naphthoflavone (BNF) treated rats. Substitutions of the hydrogens in the methyl group of 2,4-DAT with deuterium resulted in a decrease in mutagenicity. Incubation of rat liver microsomes with tritiated 2,4-DAT in the presence of NADPH led to the formation of irreversibly bound products to microsomal protein. The rates of binding were not increased using microsomes from PB or BNF-treated rats and was not altered by deuterium substitution in the methyl group. Addition of superoxide dismutase, glutathione (GSH) or rat liver supernatant reduced 2,4-DAT irreversible binding, whereas 2,4-DAT mutagenicity was unaffected by superoxide dismutase addition. Injection of tritiated 2,4-DAT 100 mg/kg to rats lead to its irreversible binding to liver protein and ribosomal RNA and to kidney protein in vivo, again protein binding was not increased after prior treatment with PB or BNF. No irreversible interaction of tritiated 2,4-DAT with DNA either in vitro or in vivo could be demonstrated.

Animals↗
PubMed1979

Cytotoxic effects of tris(2,3-dibromopropyl)phosphate and 2,4-diaminoanisole.

The flame retardant tris(2,3-dibromopropyl)phosphate (Tris-BP) and the hair-dye component 2,4-diaminoanisole (2,4-DAA) were studied by possible cytotoxic effects in rat hepatoma cells grown in culture and in suspensions of isolated rat hepatocytes. Cell growth of Reuber cells was inhibited by 50% at 50 microgram/ml Tris-BP and 20 microgram/ml 2,4-DAA, respectively. At 200 microgram/ml Tris-BP protein synthesis in Reuber cells was reduced by 40%, whereas 50% inhibition of protein synthesis in isolated hepatocytes was seen at 100 microgram/ml. IC50 of 2,4-DAA with respect to protein synthesis was found at 400 microgram/ml in Reuber cells and at 3600 microgram/ml in MH1C1 cells, whereas in the isolated hepatocytes IC50 was 650 microgram/ml. DNA synthesis was inhibited by 50% at 225 microgram/ml Tris-BP in Reuber cells. At 500 microgram/ml 2,4-DAA DNA synthesis in Reuber and MH1C1 cells was inhibited by more than 80%.

Animals↗
PubMed1979

Mutagenic activation of tris(2,3-dibromopropyl)phosphate: the role of microsomal oxidative metabolism.

The flame retardant tris(2,3-dibromopropyl)phosphate (Tris-BP) is converted to products which are mutagenic for Salmonella typhimurium TA 100 in the presence of rat liver microsomes, NADPH and oxygen. Other bromopropyl-compounds were also mutagenic; 2,3-dibromopropene and 2,3-dibromopropionic acid were directly mutagenic, whereas 2,3-dibromopropanol and tris(2-bromopropyl)phosphate were weakly mutagenic after addition of liver microsomes and cofactors. Typical in vivo and in vitro inhibitors of cytochrome P-450 inhibited Tris-BP mutagenicity. The effects of inducers of cytochrome P-450 on Tris-BP mutagenicity was dependent on the concentration of mutagen and microsomal protein in the assay, indicating complexity in the kinetics involved when dealing with possible multiple pathways that lead to mutagenicity. Addition of glutathione strongly inhibited Tris-BP mutagenicity. It is suggested that Tris-BP is oxidized to a reactive electrophile, possibly the 2-keto derivative, which could react with nucleophilic groups in DNA and thus lead to mutagenic events.

1-Propanol↗
PubMed1979

Metabolism and activation of 2-acetylaminofluorene in isolated rat hepatocytes.

The metabolism of 2-acetylaminofluorene (AAF) as well as the activation of AAF to covalently bound and mutagenic intermediates were studied in isolated rat hepatocytes. The cell system readily formed oxidized, deacetylated, and conjugated AAF metabolites. Pretreatments of animals with the inducer beta-naphthoflavone led to increases in phenolic and conjugated as well as covalently protein-bound products. Addition of 4-nitrophenol, a substrate for conjugation, increased the levels of free phenols and inhibited the formation of water-soluble metabolites. At the same time, the rates of covalent protein binding were decreased. Formation of 9-hydroxy-2-acetylaminofluorene could also be demonstrated. The pathway leading to this alicyclic hydroxylated AAF metabolite was not induced by prior beta-naphthoflavone treatment, nor was it inhibited by 4-nitrophenol addition. The cells converted AAF as well as aminofluorene and 2,4-diaminoanisole to mutagenic intermediates which were released into the incubation medium. 2-Aminofluorene was considerably more mutagenic than was AAF in this system. Addition of microsomes increased the mutagenicity of AAF, but not that of 2-aminofluorene or 2,4-diaminoanisole, presumably by deacetylation of N-hydroxy-2-acetylaminofluorene to N-hydroxy-2-aminofluorene.

2-Acetylaminofluorene↗
PubMed1978

Covalent binding of 2,4-diaminoanisole and 2,4-diaminotoluene in vivo.

We have studied the activation of 2,4-diaminoanisole (2,4-DAA), a mutagenic hair-dye component, and 2,4-diaminotoluene (2,4-DAT), a hepatocarcinogen, to products which blind covalently to tissue macromolecules. Four hours after a dose of 100 mg/kg ring-labeled 3H-2,4-DAA, 0.30 nmol is found covalently bound per mg liver protein. This amount is increased by 83% after phenobarbital pretreatment, and by 43% after beta-naphthoflavone-pretreatment. Almost the same degree of binding is seen in kidneys. Subcellular fractionation of livers shows that most of the bound material is in the microsomal fraction. Similar levels of covalent protein binding is seen after administering ring-labeled 3H-2,4-DAT. No significant binding to DNA in vitro or in vivo could be demonstrated using 3H-2,4-DAA or 3H-2,4-DAT, whereas 3H-2,4-DAT is found to covalently bind to hepatic RNA.

Animals↗