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Biomedical subjects

C M King

Publications and source records attributed to C M King.

At least 127 records · Page 7Linked to original sources
PubMed1984

Mutagenicity of azo dyes following metabolism by different reductive/oxidative systems.

The mutagenic activity of a group of diazo dyes based on benzidine and its congeners was compared following metabolic activation of the dyes through sequential reduction and oxidation. The dyes were reduced by incubating them with either a suspension of rat cecal flora or a hamster S9 mix supplemented with flavin mononucleotide. The products of dye reduction were then subjected to oxidative metabolism by either Aroclor-induced rat liver S9 or by hamster liver S9; the resultant mutagenic activity was assayed with Salmonella typhimurium TA1538. Fifteen of the 17 compounds tested were mutagenic, and the degree of mutagenicity was affected by the activity of both the reduction and oxidation systems used. Purified dyes required a reductive step to become mutagenic, but several of the crude dyes did not. All the positive compounds, however, were more mutagenic when the reduction step was included. The mutagenicity of the purified dyes was equal to or greater than that of an equimolar amount of benzidine or appropriate benzidine congener. For the crude dyes, there were no consistent quantitative relationships between the mutagenicity of the dye and that expected from the benzidine moiety.

Animals↗
PubMed1984

A double-blind study of superficial radiotherapy in chronic palmar eczema.

The effect of superficial radiotherapy as an adjunct to topical therapy in recalcitrant chronic symmetrical palmar eczema was assessed in fifteen patients by randomly allocating active treatment to one palm while the other, which received simulated therapy, served as a control. There was a significantly better response to active treatment at 1 month but this difference was no longer apparent at 3 and 6 months.

Adult↗
PubMed1984

Multicentric pigmented Bowen's disease of the genitalia associated with carcinoma in situ of the cervix.

A case of multicentric pigmented Bowen's disease in a 45 year old woman with a previous history of carcinoma of the cervix is described. The two conditions may have a common pathogenesis, and a preceding viral infection with herpes simplex or human papillomavirus could be of aetiological relevance. Patients with multicentric pigmented Bowen's disease may be at risk of developing other tumours of the genital tract. Treatment with carbon dioxide laser proved effective.

Bowen's Disease↗
PubMed1984

Induction of rat mammary gland tumors by 1-nitropyrene, a recently recognized environmental mutagen.

1-Nitropyrene, a direct-acting mutagenic component of extracts of diesel exhaust and ambient air particulates, is one of the major nitroarenes found in products of incomplete combustion. Injection of this compound into newborn Sprague-Dawley-derived CD rats at 100 mumol/kg body weight s.c. once a week for 8 weeks induced 32 and 28% sarcomas, primarily malignant fibrous histiocytomas, at the site of injection in male and female animals, respectively. Mammary tumors, most of which were adenocarcinomas, developed distant from the site of injection in 47% of the females. Similar but lesser responses were observed in animals given one-half this dose. This carcinogenic response is consistent with the systemic effects of structurally related aromatic amines. 4-Nitrobiphenyl, given at equimolar doses, was not tumorigenic in this study.

Animals↗
PubMed1983

Prostaglandin H synthase-mediated reaction of carcinogenic arylamines with tRNA and homopolyribonucleotides.

Prostaglandin H synthase mediates the reaction of an extensive series of carcinogenic arylamines with tRNA. Structure-activity relationships suggest that benzidine is especially reactive due to extended conjugation between the 4,4'-diamino groups. In trapping experiments with homopolyribonucleotides, benzidine reacts with polyguanylic acid but 4-aminobiphenyl reacts with polycytidylic acid. The nitrenium ion of 4-aminobiphenyl (formed by N,O-acyltransferase activation of N-hydroxy-4-acetylaminobiphenyl) reacts primarily with polyguanylic acid and to a lesser extent with polyadenylic acid. The results suggest that arylamine activation by prostaglandin H synthase does not involve nitrenium ion formation.

Animals↗
PubMed1983

Conversion of Congo red and 2-azoxyfluorene to mutagens following in vitro reduction by whole-cell rat cecal bacteria.

Congo red, an azo dye derived from benzidine, and 2-azoxyfluorene, a derivative of 2-aminofluorene, were reduced during overnight incubation with a suspension of rat intestinal bacteria. High performance liquid chromatography and ultraviolet spectral analysis verified the presence of benzidine in extracts of the Congo red incubations and 2-aminofluorene in extracts of the 2-azoxyfluorene incubations. Extracts of the Congo red incubations were mutagenic toward Salmonella typhimurium TA1538 in the presence of a post-mitochondrial activating system, but Congo red was not mutagenic without this reductive pretreatment. Thus, the utility of the Ames test in screening for potential mutagens may be expanded by a reductive pretreatment utilizing cecal bacteria.

Animals↗
PubMed1983

Oral promethazine hydrochloride in ethylenediamine-sensitive patients.

A study of 12 patients with allergic contact sensitivity to ethylenediamine has shown that exposure to the oral antihistamine promethazine hydrochloride (Phenergan) did not result in an exacerbation or recrudescence of eczema. This would suggest that promethazine may be safely administered to ethylenediamine-sensitive patients contrary to advice given in some of the dermatological literature.

Administration, Oral↗
PubMed1983

Acetylation, deacetylation and acyltransfer.

N-Substituted aromatic compounds can be metabolized in most species to N-acetylated derivatives that are themselves subject to further enzymatic transformations, including hydrolysis and N,O-acyltransfer. These proceses can either potentiate or ameliorate the biological responses to these N-substituted derivatives. Decreasing the levels of metabolites, such as arylhydroxylamines may, in some systems, reduce the probability of eliciting adverse biological effects. In others, arylhydroxamic acids produced by the acetylation of arylhydroxylamines may increase their potential for metabolic activation by N,O-acyltransfer. In the rabbit, rat and perhaps other species, the acetyl CoA-dependent N-acetyltransferase is also capable of activating arylhydroxamic acids by N-O-acyltransfer. These cytosolic organotriphosphate ester-resistant enzymes can utilize arylhydroxamic acid as a donor of the acetyl moiety in the acetyl transferase reaction and apparently are capable of activating arylhydroxamic acids because of their ability to O-acetylate the arylhydroxlamine. In mice, N-acetyltransferase and N,O-acetyltransferase seem not to exhibit this relationship. Enzymes from the microsomes of a number of species are also capable of activating arylhydroxamic acids. The particulate-bound enzymes are organotriphosphate ester-sensitive deacylases that are unable to form nucleic acid adducts on incubation with N-methoxy-N-acetylaminoarenes, substrates that are not capable of activation by N,O-acyltransfer. Thus, depending on the specificity of the enzymes involved, N-substituted aromatic compounds may be activated by N,O-acyltransfer during both the acetylation and deacylation process. The influence of this activation in the carcinogenic process is the object of continuing investigation.

Acetyl-CoA C-Acetyltransferase↗
PubMed1982

Effect of acetylated and deacetylated 2-aminofluorene adducts on in vitro DNA synthesis.

We have constructed primed phi X174 DNA templates containing either acetylated or deacetylated aminofluorene adducts at the C-8 position of guanine. T4 DNA polymerase terminates synthesis one nucleotide before the acetylated adducts but incorporates an additional nucleotide opposite the deacetylated guanylaminofluorene. These observations can be explained by the known preferred conformations of the acetylated and deacetylated guanosinylaminofluorene nucleosides--the former favoring the syn conformation (so that in DNA the guanine is displaced from the helix by the fluorene ring) and the latter preferring the anti conformation (which allows normal base pairing of the guanine with cytosine). A similar differentiation between the two adducts was found with Escherichia coli DNA polymerase I. In contrast, avian myeloblastosis virus (AMV) reverse transcriptase, which terminated with a nucleotide inserted opposite the acetylated adducts, was less able to do so at the deacetylated adducts. The nucleoside incorporated by AMV reverse transcriptase opposite the acetylated adduct was exclusively cytidine, which suggests regular base pairing with the reacted guanosine nucleoside in the anti conformation; however, synthesis was completely blocked and unable to continue beyond this point. The differences between the termination patterns of the prokaryotic enzymes and AMV reverse transcriptase indicates that specific properties of a replicating polymerase can influence the conformation of a reacted nucleoside in the DNA, thus altering its recognition and possibly its mutagenic activity.

2-Acetylaminofluorene↗
PubMed1982

Sulfotransferase and deacetylase in normal and tumor-bearing liver of CD rats: autoradiographical studies with N-hydroxy-2-acetylaminofluorene and N-hydroxy-4-acetylaminobiphenyl in vitro and in vivo.

Slices of liver from CD rats were evaluated by autoradiography after exposure to N-hydroxy-2-acetylaminofluorene (N-hydroxy-AAF) labeled in the acetyl moiety with tritium. These in vitro experiments showed that the incorporation of the acetyl group of N-hydroxy-AAF was a sulfate-dependent enzymatic process in livers from male rats. Livers from females, and hyperplastic nodules and carcinomas induced in the livers of males, were essentially incapable of carrying out this reaction. The results of these in vitro experiments were compared with those obtained with liver sections from a male CD rat exposed in vivo to the tritiated N-hydroxy-AAF. A close relationship between covalent binding and necrosis was demonstrated by the observation that the acetyl moiety of N-hydroxy-AAF was preferentially incorporated into the periportal area, the same area in which liver necrosis occurs after a single injection of the hydroxamic acid. These data offer a biochemical rationale for the relative sensitivities of these cells to the toxic effects of N-hydroxy-AAF and its parent amide. There were no differences in the incorporation of ring-labeled N-hydroxy-4-acetylaminobiphenyl with respect to the sex of the animal or to the morphological characteristics of the tissue. The inhibition of the formation of these adducts by paraoxon suggests that they resulted from the action of deacetylases in the endoplasmic reticulum.

2-Acetylaminofluorene↗