University of Surrey

Test tubes in the lab Research in the ATI Dance Research

Studies on the teratogenicity of methoxyacetic acid.

Rawlings, Sally Jeanette. (1987) Studies on the teratogenicity of methoxyacetic acid. Doctoral thesis, University of Surrey (United Kingdom)..

[img]
Preview
Text
10804391.pdf
Available under License Creative Commons Attribution Non-commercial Share Alike.

Download (9MB) | Preview

Abstract

The teratogenicity of methoxyacetic acid (MAA) was studied using rat whole-embryo and limb bud micromass cultures. MAA and some related alkoxy acids were direct-acting teratogens in both systems. Structure-activity investigations produced the same rank-order of potency; methylthioacetate > MAA > ethoxyacetate. All other compounds tested were either much less effective or inactive. In whole embryo culture the uptake of MAA was rapid, appeared to be by simple diffusion, and to be determined by pH partitioning. MAA accumulated in the relatively alkaline conceptus; for example, the exocoelomic fluid concentration was 1.7 fold that of the medium. In micromass cultures uptake was also dependent on pH partitioning, hence MAA was more effective in Hams F-12 (pH 7.1) medium than in DMEM (pH 7.6). MAA did not appear to be metabolised by the rat embryo in culture. After a 48 h exposure, radiolabel derived from MAA was not incorporated into macromolecular fractions (lipid, RNA, DNA, or protein) of the developing conceptus. Also, HPLC analysis of the acid-soluble phase of embryonic tissue and media samples did not reveal methoxyacetylglycine or any other known MAA metabolite. Using both culture systems it was shown that MAA did not evoke its teratogenic response via an initial inhibitory effect on either DNA or protein synthesis, glycolysis, nor the incorporation of acetate or sulphate. In addition, MAA did not inhibit yolk-sac pinocytosis. The first day of a 6 day micromass culture was most sensitive to MAA treatment. The protein content and cell number of treated cultures were severely reduced by 24 h, indicating cell death and/or cell loss. Thus, biochemical measurements taken at 24 h or later may reflect secondary, rather than initial, insults. Replating of MAA-treated micromass cultures (after a 24 h exposure), to re-establish normal cell density, did not restore the ability to form chondrogenic foci. The inhibition of differentiation was not, therefore, freely reversible nor the result of a decreased cell density, but may be due to selective cytotoxicity against the sub-population of pre-chondrogenic cells.

Item Type: Thesis (Doctoral)
Divisions : Theses
Authors :
NameEmailORCID
Rawlings, Sally Jeanette.
Date : 1987
Contributors :
ContributionNameEmailORCID
http://www.loc.gov/loc.terms/relators/THS
Additional Information : Thesis (Ph.D.)--University of Surrey (United Kingdom), 1987.
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/847930

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