In vivo studies with [methyl-³H]-thymidine regarding the effect of methyl donors cocktail in cancer therapy

Abstract

The aim of this study was to evaluate the effect of methyl donor biovectors as cocktail formulation in cancer therapy. Based on our previous results regarding the pharmacokinetic of [Methyl-¹⁴C] Choline and [Methyl-³H] S-Adenosyl-Methionine (SAM) in presence of Folic Acid and their properties in the regulation of transmethylation metabolism, a cocktail solution of SAM, Choline and Folic Acid was prepared taking into account the previosly established molar ratios. The studies regarding the therapeutic effect of cocktail solution were effectuated on RS1 tumor bearing animal models. For evaluation of tumour cell proliferation we used the [Methyl-³H]-Thymidine with 25 Ci/mmol specific activity. The biodistribution studies were perfomed on untreated and treated tumuor bearing animals. The animal lots dedicated for treatment with methyl donors cocktail were treated with 200 μL cocktail for 4 days. After finishing the treatment, both untreated and treated animal lots were injected with 150 μCi [Methyl-³H]-Thymidine. Biodistribution studies were performed at 2, 4 and 8 hours post injection. The biodistribution results showed that at tumor level the uptake of [Methyl-³H]Thymidine is higher in the untreated animals (0.78%ID/g at 2 h, 1.07%ID/g at 4 h and 1.35%ID/g at 8 h) than in treated animals (0.06%ID/g at 2 h, 0.11%ID/g at 4 h and 0.13%ID/g at 8 h). The results regarding the Homocysteine levels in investigated animals show a decreasing of Homocysteine concentration up to normal values for treated animals.