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Thiazolidine-4-Carboxylate and 2-Phenylthiazolidine-4-Carboxylate are Active as Cysteine Precursors but have no Effect on Growth of a Methionine-Dependent Tumor in Rats

Laboratoire de Nutrition et Cancérologie Expérimentale, Institut du Cancer, 34094 Montpellier Cedex 5, France

Diets with partial replacement of sulfur amino acids by thiazolidine-4-carboxylate or 2-phenylthiazolidine-4-carboxylate were fed to normal and to rhabdomyosarcoma-bearing rats (methionine-dependent tumor) to evaluate their efficacy as cysteine precursors and as antitumor agents. Food intake, weight gain, food efficiency and plasma albumin and plasma sulfur amino acid concentrations were not different when these diets were compared with isosulfurous diets containing either methionine or N-acetylcysteine. 2-Phenylthiazolidine-4-carboxylate induced a lower plasma glutathione (GSH) level than the latter diets. Tumor-bearing rats had lower plasma GSH concentration. A negative linear relationship was found between plasma GSH levels and tumor weight and also the tumor weight: body weight ratio. This could mean that the tumor becomes the most important organ in the uptake of GSH. However, there was also a significant positive correlation between plasma GSH and albumin, suggesting a reduced GSH hepatic synthesis due to amino acid uptake by the tumor. There were no differences in tumor growth among rats receiving diets containing N-acetylcysteine, thiazolidine-4-carboxylate or 2-phenylthiazolidine-4-carboxylate.

KEY WORDS: • cysteine • thiazolidine • glutathione • rhabdomyosarcoma • rats

Manuscript received 22 January 1991. Revision accepted 22 May 1991.