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R Easterling

Publications and source records attributed to R Easterling.

7 recordsLinked to original sources
PubMed1984

Mutagenicity of cyclopenta-fused isomers of benz(a)anthracene in bacterial and rodent cells and identification of the major rat liver microsomal metabolites.

The microsomal metabolites and mutagenic activity of four cyclopenta-fused benz(a)anthracenes, benz(j)aceanthrylene [B(j)A], benz(e)aceanthrylene [B(e)A], benz(l)aceanthrylene [B(l)A], and benz(k)acephenanthrylene [B(k)A], have been studied. Aroclor 1254-induced rat liver microsomes metabolized B(j)A to B(j)A-1,2-dihydrodiol, B(j)A-9,10-dihydrodiol, B(j)A-11,12-dihydrodiol, and 10-hydroxy-B(j)A; B(e)A-1,2-dihydrodiol, B(e)A-3,4-dihydrodiol, and B(e)A-5,6-dihydrodiol; B(l)A to B(l)A-1,2-dihydrodiol, B(l)A-4,5-dihydrodiol, and B(l)A-7,8-dihydrodiol; and B(k)A to B(k)A-4,5-dihydrodiol and B(k)A-8,9-dihydrodiol. With each polycyclic aromatic hydrocarbon, metabolism occurred on the cyclopenta ring. All four isomers were active as gene mutagens in Salmonella typhimurium and in Chinese hamster V79 cells. In the S. typhimurium mutation studies, using Aroclor 1254-induced rat liver S9, B(j)A, B(e)A, and B(l)A required significantly less microsomal protein for maximal mutation response than B(k)A and B(a)P, suggesting a one-step activation mechanism, presumably on the cyclopenta-fused ring. B(j)A, B(e)A, and B(l)A were significantly more mutagenic than B(k)A and B(a)P in S. typhimurium. In the Aroclor 1254-induced rat liver S9-mediated V79 mutagenesis system, all four isomers were active, with B(l)A the most active. When Syrian hamster embryo cells were used as the metabolic activation component for V79 cells, only B(l)A produced a significant response and was equivalent in activity to B(a)P. A helical configuration for B(l)A is inferred from the identification of two trans-B(l)A-1,2-dihydrodiols, syn and anti, which have been synthesized, separated, and characterized. The metabolically formed dihydrodiol is anti-trans-B(l)A-1,2-dihydrodiol, and experimental evidence suggests that the metabolically formed B(l)A-1,2-oxide is the anti-isomer. Synthetic B(l)A-1,2-oxide was found to be a direct-acting mutagen in S. typhimurium and Chinese hamster V79 cells and is estimated to account for up to 40% of the mutagenic activity of the parent hydrocarbon. Therefore, certain cyclopenta-ring fusions on benz(a)anthracene appear to markedly increase its genotoxic and carcinogenic activities.

Animals↗
PubMed1983

Benz[j]aceanthrylene: a novel polycyclic aromatic hydrocarbon with bacterial mutagenic activity.

Initial studies on the mutagenicity and metabolism of a novel cyclopenta-PAH, benz[j]aceanthrylene, are reported in the Salmonella bacterial system. The spectrum of activity of benz[j]aceanthrylene over the 5 Ames tester strains is similar to that of benzo[a]pyrene, and the dose-response curves for strain TA98 are comparable. Like other biologically active PAH, benz[j]aceanthrylene is a frame-shift mutagen requiring metabolic activation. An interesting feature of the S9 dependence of activity is the low concentration (congruent to 10-fold smaller than for benzo[a]pyrene) at which optimal activity is observed. The 1,2-dihydro-1,2-diol (product of metabolism of the cyclopenta-ring) appears to be the predominant metabolite, and implicates the 1,2-oxide as the ultimate mutagenic species.

Methylcholanthrene↗
PubMed1983

Reanalysis and clarification of the structures of alpha-naphthoflavone dihydrodiols formed by uninduced and induced rat liver microsomes from Charles River CD and Sprague-Dawley rats.

The structures of alpha-naphthoflavone (ANF) dihydrodiols formed by uninduced and induced rat liver microsomes are identified by conversion of the metabolically formed ANF-dihydrodiols to the corresponding phenols. Comparison of these phenols with synthetic standards provides an unambiguous method for structural identification. The results of these studies are that hepatic microsomes from uninduced or phenobarbital, Aroclor-1254, 3-methylcholanthrene, or 5,6-benzoflavone induced Sprague-Dawley or Charles River CD rats each produce a major and a minor ANF-dihydrodiol identified as ANF-7,8-dihydrodiol and ANF-5,6-dihydrodiol, respectively.

Animals↗
PubMed1982

Inhibition of benzo(a)pyrene monooxygenase by alpha-naphthoflavone may be partially mediated by the metabolite 9-hydroxy-alpha-naphthoflavone.

alpha-Naphthoflavone (ANF) inhibits beta-naphthoflavone-induced rat liver microsomal benzo(a)pyrene metabolism and is transformed by these microsomes into alpha-naphthoflavone metabolites. We determined the inhibitory effect on benzo(a)pyrene (B(a)P) metabolism of several of these metabolites and of 6-methoxy-ANF, using beta-naphthoflavone-induced rat liver microsomes. 9-Hydroxy-ANF was the most active inhibitor (I50 = 1.47 microM) and was metabolized from ANF by these hepatic microsomes in concentrations which are inhibitory. Therefore, 9-hydroxy-ANF a microsomal metabolite of ANF, may play a role in the inhibition of B(a)P oxidation by ANF.

Animals↗
PubMed1967

Detection of clostridial hemolysin formed in vivo.

Experimental clostridial myonecrosis closely resembling gas gangrene was produced in goats by the intramuscular injection of washed clostridia suspended in adrenalin. The preparation provides a model for the study of clostridial myonecrosis that is relatively isolated from preceding trauma. A new test for the demonstration of clostridial exotoxins, the hemolysin indicator plate test, was described. This test gave reliable results within 6 hr, and only minute quantities of test material were required. Application of this test to would exudates of goats with experimental clostridial myonecrosis demonstrated the presence of the gamma toxin of Clostridium novyi, alpha toxin of C. septicum, and the alpha toxin of C. perfringens in exudates from animals injected with washed Clostridium bacilli suspended in adrenalin. Exudates from goats injected with C. perfringens were lethal for mice and produced necrosis of guinea pig skin typical of C. perfringens. The convincing demonstration of clostridial exotoxins formed in vivo in this experimental model could be the basis for definition of clostridial exotoxin actions which have evaded study in the past.

Animals↗
PubMedDate not supplied

Digitalis toxicity.

Digitalis toxicity is a frequently encountered clinical problem. Drug interactions leading to digitalis toxicity are very common. Within this group, the interaction of digitalis and verapamil is increasingly recognized as an important cause of digitalis toxicity. The use of digoxin-binding antibodies represents a significant advance in the treatment of this problem and can be lifesaving in the setting of massive overdose. A case report of digitalis toxicity and a review of this problem and its treatment are presented.

Digitalis Glycosides↗