Transformation of cultured mouse mammary glands by aromatic amines and amides and their derivatives.
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The antiarrhythmic activity of the compound N-(trans-3-hydroxy-1,2,3,4-tetrahydro-2-naphthyl)-N-(3-oxo-3-phenyl-2-methylpropyl)-piperazine hydrochloride, referred to as P11, is studied on anaesthesized cats and Wistar albino rats, as well as on non-anaesthesized rabbits. Four types of experimental arrhythmia are used--with BaCl2, with chloroform-adrenaline, with strophantine G and with aconitine. The compound P11 is introduced in doses of 0.25 and 0.50 mg/kg intravenously and 10 mg/kg orally. The compound manifests antiarrhythmic activity in all models of experimental arrhythmia used, causing greatest inhibition on the arrhythmia induced by chloroform-adrenaline (in 90 per cent) and with BaCl2 (in 84 per cent). The results obtained are associated with the beta-adrenoblocking and with the membrane-stabilizing action of the compound.
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A method is described for the simultaneous quantitation of trace amounts of alpha- (alpha-NA) and beta-naphthylamines (beta-NA) with detectability in the 0.1 ppb range and sensitivity of 50 picomoles in certified food grade amaranth (FD&C Red No. 2; C.I. Food Red 9; CI 16185). The amaranth sample is extracted with benzene, and the evoporated residue is derivatized with perfluorooctanoic anhydride. The resulting derivatives are separated by gas-liquid chromatography and identified and quantitated by mass spectrometric monitoring of the m/e at 539.04. The method was used for quantitation of alpha-NA and beta-NA in randomly chosen samples of amaranth. Of 11 samples from different manufacturers, 5 were free of the beta-isomer; the remaining samples contained up to 1.2 ppb beta-NA. The concentration of alpha-NA ranged from no detectable amount to 970 ppb; the majority of the samples contained less than 7 ppb.
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Seven different strains of Staphylococcus epidermidis and one strain of S. aureus were catagorized by their aminopeptidase activity. Eight different profiles were obtained: five profiles for S. epidermidis biotype 4 (each representing a different known serotype), two profiles for S. epidermidis biotype 1 (one for each strain used) and one for the strain of S. aureus used. Despite some similarities, distinct patterns of the hydrolysis of 22 different amino acid-beta-naphthylamides were evident for each individual strain. The evaluation of aminopeptidase profiles provides another means for distinguishing between strains of the same species and can, therefore, be used advantageously and in combination with serotyping as an epidemiological tool.
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A survey of many of the known or suspected causative agents in the etiology of bladder cancer is presented. In several instances, a comparison of the epidemiological evidence and the results of animal bioassays is made. Difficulties in the interpretation of animal studies and the extrapolation of animal data to estimate human risk is discussed. Each class of chemicals, such as the aromatic aminatic amines or the non-nutritive sweetners, presents its unique problems when attempts are made to evaluate its potential as a causative agent in the etiology of bladder cancer.
Four days after single i.p. administrations of 2-aminonaphthalene to C3H mice, the liver content of reduced glutathione and the liver microsomal cytochrome P-450 O-demethylation activity were decreased. No changes were observed in oxidized glutathione.
A study on the effects of hyperthermia on B.N.A. induced bladder carcinomas of the dog has been carried out since 1966. The hyperthermic treatment has been performed directly in the bladder using an original equipment especially designed. In a large majority of the animals definite cancericidal changes have been shown. The most favorable results were obtained in the treatment of carcinomas not infiltrating the muscular layer of the bladder. In these cases malignant recurrency was not shown up to five years after treatment. Good palliative effect is also refferred in the treatment of advanced bladder carcinoma of the man.
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It is now well established that the interaction of multiple environmental factors may increase the incidence of some human cancers more than exposure to a single carcinogen. With an in vivo experimental rat model, we have demonstrated a synergistic effect in bladder carcinogenesis between a subcarcinogenic dose of the strong bladder carcinogen, N-methyl-N-nitrosourea, and saccharin- or cyclamate-containing diets. If these artificial sweeteners are capable of interacting with other environmental bladder carcinogens, their potential for increasing the incidence of human bladder cancer is greater than many more potent chemical carcinogens, because of their wide distribution as food additives to all sections of the population. Retrospective epidemiology shows no evidence of such risk from saccharin at current levels of consumption. No comparable studies are available for cyclamate, which was consumed in greater quantities but for relatively few years. It is emphasized that it is possible for interaction between multiple factors to contribute to the incidence of human bladder cancer as it does in other human organs and in other animal species.
Circular dichroism curves have been measured for phthaloyl-, maleyl- and itaconyl-derivatives of a number of amines having a general formula R--CH(NH2)--R' (in which R and R' are alkyl-, aryl- or cyclohexyl-groups) and of 1,2,3,4-tetrahydro-1-naphthylamine and 1,2,3,4-tetrahydro-2-naphthylamine. We conclude that the determination of absolute configuration of amines examined can be made on the basis of C.D. curves of their phthaloyl-, maleyl- and itaconyl-derivatives, referring to that portion of the curve relating to the imide chromophore absorption.
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