Comparative study of the effect of ochratoxin A analogues on yeast aminoacyl-tRNA synthetases and on the growth and protein synthesis of hepatoma cells

• Published in: Toxicology letters Vol. 19; no. 3; p. 217
• Main Authors: Creppy, E E, Kern, D, Steyn, P S, Vleggaar, R, Röschenthaler, R, Dirheimer, G
• Format: Journal Article
• Language: English
• Published: Netherlands 01.12.1983
• Subjects: Amino Acyl-tRNA Synthetases - antagonists & inhibitors; Animals; Cells, Cultured; Liver Neoplasms, Experimental - metabolism; Neoplasm Proteins - biosynthesis; Ochratoxins - pharmacology; Rats; Saccharomyces cerevisiae - drug effects
• ISSN: 0378-4274
• DOI: 10.1016/0378-4274(83)90122-4

Ochratoxin A (OTA), a naturally occurring mycotoxin of Aspergillus and Penicillium species, consists of a 5' chlorinated dihydromethyl isocoumarin linked to L,beta-phenylalanine by an alpha-amide bond. 8 analogues of OTA were prepared in which the phenylalanine was always substituted by another amino acid. The effects of these analogues on yeast tRNA amino acylation reaction and on growth and protein synthesis of hepatoma culture cells were compared with those of OTA. In addition, Ochratoxin B (OTB) and ochratoxin alpha (OT alpha) were examined. All the analogues of OTA had inhibitory effects in the 3 test systems, although to a lesser degree than OTA. The degree of inhibition depended on the kind of substituted amino acid, the tyrosine, valine, serine and alanine analogues being most effective, in contrast to the proline analogue. OTB and OT alpha were ineffective.