PubMed Health⌕ Search

Biomedical subjects

E C Miller

Publications and source records attributed to E C Miller.

At least 19 recordsLinked to original sources
PubMed1979

The mutagenicities of safrole, estragole, eugenol, trans-anethole, and some of their known or possible metabolites for Salmonella typhimurium mutants.

Safrole, estragole, anethole, and eugenol and some of their known or possible metabolites were tested for mutagenic activity for S. typhimurium TA1535, TA100, and TA98. Highly purified 1'-hydroxyestragole and 1'-hydroxysafrole were mutagenic (approximately 15 and 10 revertants/micromole, respectively) for strain TA100 in the absence of fortified liver microsomes; trans-anethole and estragole appeared to have very weak activity. 3'-Hydroxyanethole was too toxic for an adequate test. Supplementation with NADPH-fortified rat-liver microsomes and cytosol converted 3'-hydroxyanethole to a mutagen(s) and increased the mutagenic activities for strain TA100 of 1'-hydroxyestragole, 1'-hydroxysafrole, estragole, and anethole. No mutagenicity was detected for safrole or eugenol with or without added NADPH-fortified liver preparations. The electrophilic 2',3'-oxides of safrole, 1'-hydroxysafrole, 1'-acetoxysafrole, 1'-oxosafrole, estragole, 1'-hydroxyestragole, and eugenol showed dose-dependent mutagenic activities for strain TA1535 in the absence of fortified liver microsomes. These mutagenic activities ranged from about 330 revertants/micromole for 1'-oxosafrole-2',3'-oxide to about 7000 revertants/micromole for safrole-2',3'-oxide. The arylalkenes, their hydroxylated derivatives, or their epoxides did not show mutagenic activity for strain TA98, except for 1'-oxosafrole-2',3'-oxide, which had weak activity. Since the arylalkenes are hydroxylated and/or epoxidized by hepatic microsomes, hydroxy and epoxide derivatives appear to be proximate and ultimate mutagenic metabolites, respectively, of the arylalkenes.

Anisoles↗
PubMed1979

Promotion by dietary phenobarbital of hepatocarcinogenesis by 2-methyl-N,N-dimethyl-4-aminoazobenzene in the rat.

The hepatocarcinogenicity of 2-methyl-N,N-dimethyl-4-aminoazobenzene, previously shown to be noncarcinogenic in adult rats in the absence of further treatment, was observed by following a 1- to 6-week period of feeding this dye to weanling rats with the dietary administration of 0.05% phenobarbital for up to 70 weeks. Many large hepatocellular carcinomas developed in the phenobarbital-treated animals by 72 weeks, whereas a very small number of tiny neoplastic nodules, including one carcinoma, were seen in the rats not given this drug. This study suggests that the use of promoting agents, following the short-term administration of weak carcinogens for the liver, can be useful in demonstrating the initiating activity of such compounds. This system may be useful in the identification of such agents in the environment.

Animals↗
PubMed1979

The N-hydroxy metabolites of N-methyl-4-aminoazobenzene and related dyes as proximate carcinogens in the rat and mouse.

The carcinogenicities for rats and mice of N-methyl-4-aminoazobenzene (MAB) and its hepatic microsomal metabolite N-hydroxy-N-methyl-4-aminoazobenzene (N-hydroxy-MAB) were compared under several conditions. N-Ethyl-4-aminoazobenzene, 4-aminoazobenzene, and their N-hydroxy derivatives were also included in some of the assays. About 25% of the rats given MAB or N-hydroxy-MAB (3 to 5 mmol/kg body weight) by stomach tube over a 5-week period developed hepatic tumors by 18 to 22 months. Similarly treated rats subsequently given phenobarbital in the drinking water until the termination of the experiment developed about twice as many hepatic tumors. N-Hydroxy-MAB, administered p.o., but not MAB, also induced multiple papillomas and extensive carcinomas of the forestomach in approximately 50% of the rats. Only low incidence of hepatocellular carcinomas occurred in partially hepatectomized rats given a single i.p. injection of 180 mumol/kg body weight of MAB or N-hydroxy-MAB with or without subsequent administration of phenobarbital. Although repeated s.c. doses of N-benzoyloxy-N-methyl-4-aminoazobenzene induced sarcomas at the injection site in 90% of the rats, only 3 of 20 rats developed sarcomas at the site of s.c. injections of N-hydroxy-MAB. N-Ethyl-4-aminoazobenzene, 4-aminoazobenzene, and their N-hydroxy derivatives did not induce significant numbers of tumors in any of the above assay systems. Administration to preweaning male mice of MAB, N-hydroxy-MAB, N-hydroxy-N-ethyl-4-aminoazobenzene, and N-hydroxy-4-aminoazobenzene resulted in high incidences and high multiplicities of hepatic tumors (averages of 5 to 7 tumors/mouse) within 1 year. N-Ethyl-4-aminoazobenzene and 4-aminoazobenzene also induced hepatic tumors under the same conditions, but they were less active. These data support the conclusion that the N-hydroxy metabolites of these aminoazo dyes are proximate carcinogens.

Age Factors↗
PubMed1979

[The toxoplasmin skin test (st) - a safe method to reveal endured contact with toxoplasma gondii? (author's transl)].

Toxoplasmin skin tests were applied to 4.341 pregnant women, between August 1975 and December 1977, and 30 per cent of them were serologically tested by means of DT and FR. Findings were in fair agreement in 87 per cent of all cases. This result was compared to similar examinations conducted earlier in the past. Discrepancies in excess of 30 per cent were quoted elsewhere in literature. Possible causes are discussed in greater detail. - A clearcut correlation was found to exist between the intensity of dermal response to toxoplasmin skin tests and agreement between such tests, on the one hand, and serological results, on the other. That agreement, remarkably, followed a linear correlation with the age of the pregnant women concerned. The gaps between responses widened along with decreasing age. - Differences between negative ST and serological tests were recorded from as much as 27 per cent. In such cases, serological confirmation should be sought immediately. Serological verification is considered to be essential to all poor positive responses to ST, defined by the author as erythema of the skin below 10 mm in diameter, where the discrepancy figure had been nearly 28 per cent. The amount of agreement regarding skin responses above 10 mm in diameter was 98.6 per cent, an acceptable magnitude. - With all the above limitations, ST is an uninvolved and inexpensive screening method by which to detect endured toxoplasmosis. It is, therefore, suitable for proper selection, particularly at the beginning of pregnancy.

Female↗
PubMed1978

Reduced nicotinamide adenine dinucleotide phosphate-dependent formation of 2,3-dihydro-2,3-dihydroxyaflatoxin B1 from aflatoxin B1 by hepatic microsomes.

2,3-Dihydro-2,3-dihydroxyaflatoxin B1 (dihydrodiol) was formed as a major metabolite in the incubation of aflatoxin B1 with rat and hamster liver microsomes. The yield of the dihydrodiol was maximal at pH 6.5, was reduced nicotinmide adenine dinucleotide phosphate- and cytochrome P-450-dependent, and was increased 2- to 4-fold by pretreatment of the animals with phenobarbital; pretreatment with 3-methylcholanthrene did not alter the activity of rat hepatic microsomes. Inhibitors of epoxide hydrase did not lower the yield of the dihydrodiol in these systems. Negligible yields of the dihydrodiol were formed from aflatoxin B1 and rat liver microsomes in the presence of DNA. Little or no formation of the dihydrodiol was noted with microsomes from rat intestinal mucosa, kidney, or lung. These results further support the formation of aflatoxin B1 2,3-oxide as a major electrophilic metabolite of aflatoxin B1 in rat and hamster liver microsomal systems, since this highly reactive epoxide would be expected to hydrolyze readily to form the dihydrodiol.

Aflatoxins↗
PubMed1978

Guanyl O6-arylamination and O6-arylation of DNA by the carcinogen N-hydroxy-1-naphthylamine.

The carcinogen N-hydroxy-1-naphthylamine reacted with nucleic acids and protein under slightly acidic conditions (pH 5) to form covalently bound derivatives with 3 to 20 naphthyl residues/1000 monomer units. The level of binding was in the following order: DNA greater than polyguanylic acid greater than denatured DNA and ribosomal RNA greater than serum albumin greater than transfer RNA greater than polyadenylic acid. Reactions with nucleosides and nucleotides were not detected, and the binding of N-hydroxy-1-naphthylamine to DNA was not inhibited by the addition of nucleosides, nucleotides, methionine, or glutathione. The reaction rates were first order with respect to both DNA and N-hydroxy-1-naphthylamine concentrations. Enzymatic hydrolysis of the DNA containing naphthyl residues yielded 3 nucleoside-arylamine adducts. The major adduct was identified by chemical, ultraviolet, nuclear magnetic resonance, and mass spectrometric analyses as N-(deoxyguanosin-O6-yl)-1-naphthylamine. The other two adducts were identified as 2-(deoxyguanosin-O6-yl)-1-naphthylamine and its decomposition product. Direct evidence for acid-dependent arylnitrenium ion formation was obtained by isotope exchange upon solvolysis of N-hydroxy-1-naphthylamine in acidic H2 18O, and carbocation formation was indicated by the formation of the solvolysis products, 1-amino-2-naphthol and 1-amino-4-naphthol. These studies demonstrated the conversion of a carcinogenic N-hydroxy arylamine to electrophilic arylnitrenium ion and carbocation species that display high selectivity toward macromolecules. The roles of these electrophiles and their macromolecular adducts in the initiation of urinary bladder carcinogenesis through formation of promutagenic lesions in DNA are suggested.

1-Naphthylamine↗
PubMed1978

Vinyl carbamate as a promutagen and a more carcinogenic analog of ethyl carbamate.

Vinyl carbamate was much more active (10 to 50 times) than ethyl carbamate for the initiation of skin tumors and for the induction of lung adenomas in mice. Vinyl carbamate was also mutagenic to Salmonella typhimurium TA 1535 and TA 100 in the presence of reduced nicotinamide adenine dinucleotide phosphate-fortified rat or mouse liver mitochondrial supernatant fractions. This mutagenic activity was inhibited strongly by cytochrome P-450 inhibitors. No mutagenic activity was observed for vinyl carbamate in the absence of added liver preparations or for ethyl carbamate in the presence or absence of liver fractions. Extensive tests with sensitive methods failed to detect vinyl carbamate as a metabolite of ethyl carbamate in the mouse in vivo. However, on administration of [ethyl-1-14C;1,2-3H]ethyl carbamate to adult mice the 3H/14C ratios of the hepatic DNA-, rRNA-, and protein-adducts were similar to each other and much lower than the ratio of the administered ethyl carbamate. These data are consistent with the presence of desaturated and/or oxidized ethyl groups in the macromolecular adducts. The qualitatively similar, but much stronger, carcinogenic activity of vinyl carbamate as compared to that of ethyl carbamate suggests that the metabolic pathways of these two carbamates may converge in the formation of similar or identical electrophilic reactants that bind covalently to macromolecules in vivo and initiate carcinogenesis.

Adenoma↗
PubMed1978

Diabetic emergencies.

Diabetic emergencies include diabetic ketoacidosis, insulin-induced hypoglycemia, hyperosmolar coma and lactic acidosis. By determining the blood pressure, observing for evidence of dehydration or sweating and making a rapid qualitative assessment of blood glucose and ketonemia, the physician can usually identify the condition promptly. When adequate facilities are available, continuous intravenous insulin infusion is preferred for treatment of diabetic ketoacidosis. The nonketotic hyperosmolar state should be corrected gradually, not rapidly, in order to avoid cerebral edema.

Blood Glucose↗