Arylamines suppress their own activation and that of nitroarenes in V79 Chinese hamster cells by competing for acetyltransferases.

The effect of 2-aminofluorene (2-AF) on the toxicity of 2-aminoanthracene (2-AA) and 1,6-dinitropyrene (1,6-DNP) was studied in N-acetyltransferase-proficient V79-NHr1A2 cells genetically engineered for the expression of cytochrome P4501A2, and in wild-type V79-NH cells. 2-AA inhibited the growth of V79-NHr1A2 cells and induced the formation of micronuclei at concentrations of 0.1 to 1.0 microM, but was virtually without toxic effects at a concentration of 10 microM. Addition of 2-AF protected against the cytotoxic and genotoxic effects elicited by low concentrations of 2-AA. Half-maximum protection was observed at 0.2 to 0.5 microM 2-AF. The arylamine also prevented the cytotoxicity caused by 1,6-DNP in V79-NH cells and completely suppressed the formation of 1-acetylamino-6-nitropyrene from 1,6-DNP in these cells. The results indicate that arylamines and related N-hydroxyarylamines are substrates for the same acetyltransferase in V79-NH cells. In consequence, arylamines are capable of suppressing the activation of their proximate cytotoxic and genotoxic products in these cells and, presumably, in vivo

Antioxidant properties, anti-hepatocellular carcinoma activity and hepatotoxicity of artichoke, milk thistle and borututu

Cynara scolymus (artichoke), Silybum marianum (milk thistle) and Cochlospermum angolensis (borututu) are three plants widely used regarding hepatoprotective effects but to the best of our knowledge no anti-hepatocellular carcinoma activity has been studied in the most consumed forms: infusions and dietary supplements. Herein, antioxidant properties, anti-hepatocellular carcinoma activity and toxicity of infusions and dietary supplements of the mentioned plants were evaluated and compared. All the samples revealed antioxidant properties with EC50 values lower than the daily recommended dose, but infusions showed higher biological activity than dietary supplements. Borututu infusion gave the highest antioxidant activity (EC50 400 mu g/mL). Artichoke infusion also presented antitumour activity (GI(50) = 52 mu g/mL) but with toxicity for normal cells at a higher concentration (GI(50) = 72 mu g/mL). The antioxidant and antitumour properties were positively correlated with phenolics and flavonoids content. Overall, among the three studied species, borututu infusion proved to be the most complete sample regarding antioxidant and anti-hepatocellular carcinoma activity.The authors are grateful to the Foundation for Science and Technology (FCT, Portugal) for financial support to the research centre CIMO (PEst-OE/AGR/UI0690/2011). L. Barros also thanks to FCT, POPH-QREN and FSE for her grant (SFRH/BPD/4609/2008)