Further evidence of the usefulness of bile acids as molecules for shuttling cytostatic drugs toward liver tumors

Background/Aims: To use bile acids as shuttles for directing cytostatic dru gs toward liver tumors, the ability of the tumor to take up these compounds must be maintained. Thus, we investigated whether glycocholate (GC) deriva tives such as the fluorescent FITC-GC and the cytostatic Bamet-R2 are taken up by neoplastic tissue at different stages of chemically-induced rat live r carcinogenesis. Methods: Placental glutathione-S-transferase (GST-P) was immunohistochemica lly detected. Uptake studies were carried out on pure GST-P-positive cell c ultures, obtained by treatment with ethacrinic acid, FITC-GC, Bamet-R2. or cisplatin was administered (i,v,) to anaesthetized rats. Platinum in cultur e cells, liver and kidney was measured by flameless atomic absorption. Results: Co-localization after FITC-GC i,v, administration revealed that on ly 15% (20 weeks) and 30% (32 weeks) of GST-P-positive tissue was not able to take up FITC-GC, GC uptake was lower in GST-P-positive cells than in nor mal hepatocytes. Bamet-R2, uptake was lower than that for GC, but similar i n both cell types. The amount of Bamet-R2 or cisplatin retained by GST-P-po sitive tissue after in vivo administration was progressively increased duri ng carcinogenesis. Moreover, this amount was higher for Bamet-R2 than for c isplatin, By contrast, in the kidney, it was higher for cisplatin than for Bamet-R2, Conclusion: These results indicate that at the different stages of rat hepa tocarcinogenesis most GST-P-positive tissue is able to take up bile acid de rivatives, such as Bamet-R2.