University of Surrey

Test tubes in the lab Research in the ATI Dance Research

The biochemical toxicology of some beta-adrenergic blocking agents.

Okine, Laud K. N-A. (1981) The biochemical toxicology of some beta-adrenergic blocking agents. Doctoral thesis, University of Surrey (United Kingdom)..

[img]
Preview
Text
10804321.pdf
Available under License Creative Commons Attribution Non-commercial Share Alike.

Download (7MB) | Preview

Abstract

A number of beta-adrenergic blocking agents were examined for their in vivo effects on the rat hepatic microsomal mixed-function oxygenase system to determine their potential for microsomal enzyme induction and epigenetic carcinogenesis. The method is based on previous findings that pretreatment of rats with chemical carcinogens preferentially stimulates biphenyl 2-hydroxylase and ethoxyresorufin O-deethylase, mixed-function oxidase activities catalysed by cytochrome P-448,the form of microsomal cytochrome known to be formed by chemical carcinogens. None of the beta-adrenergic blockers studied with the exception of propranolol and pronethalol, stimulated these cytochrome P-448-mediated enzyme activities at very high dosage. Mutagenicity studies of some of these beta-adrenergic blocking agents, using the Ames' bacterial and mammalian micronucleus tests, indicated that none of these agents give rise to significant and dose-dependent increases in mutations. The numbers of Hi[s+] revertant colonies produced with or without rat S-9 activation system and the number of micronucleated polychromatic cells formed in mice were not significantly increased over the spontaneous control levels. Because of a suggestion that practolol toxicity, namely, ulceration of intestinal, nasal and oral mucosae, and the conjunctiva of the eyes may involve inhibition of mucus synthesis, the efects of several beta-adrenergic blocking agents were studied. Only practolol significantly inhibited mucus glycoprotein synthesis as measured by the rates of incorporation of radiolabelled amino acid and sugar precursors into rat gastrointestinal mucus glycoproteins. None of the other agents studied showed any effects similar to practolol. It has further been suggested that some carcinogens, tumour-promoting agents and inhibitors of glycoprotein synthesis, preferentially stimulate tissue guanylate cyclase and cyclic GMP without concomitant increases in adenylate cyclase and cyclic AMP leading to a decrease in the ratios of adenylate/guanylate cyclases and C-AMP/C-GMP. None of the beta-adrenergic blocking drugs studied were shown to preferentially stimulate tissue guanylate cyclase and C-GMP. They did give rise to concomitant increases in tissue guanylate and adenylate cyclases and decreases in the C-AMP and C-GMP concentrations. However, there was no direct relationship between the ratios of adenylate/guanylate cyclases and C-AMP/C-GMP before and after treatment with the various agents.

Item Type: Thesis (Doctoral)
Divisions : Theses
Authors :
NameEmailORCID
Okine, Laud K. N-A.
Date : 1981
Contributors :
ContributionNameEmailORCID
http://www.loc.gov/loc.terms/relators/THS
Additional Information : Thesis (Ph.D.)--University of Surrey (United Kingdom), 1981.
Depositing User : EPrints Services
Date Deposited : 22 Jun 2018 14:25
Last Modified : 06 Nov 2018 16:53
URI: http://epubs.surrey.ac.uk/id/eprint/847860

Actions (login required)

View Item View Item

Downloads

Downloads per month over past year


Information about this web site

© The University of Surrey, Guildford, Surrey, GU2 7XH, United Kingdom.
+44 (0)1483 300800