ROSEMARY COMPONENTS INHIBIT BENZO[ALPHA]PYRENE-INDUCED GENOTOXICITY IN HUMAN BRONCHIAL CELLS

The commonly used spice and flavouring agent, rosemary, derived from t he leaves of the plant Rosmarinus officinalis L., displays antioxidant properties in foods and in biological systems. Moreover, in animal mo dels rosemary components were found to inhibit the initiation and tumo ur promotion phases of carcinogenesis. In this work, we studied the me chanisms by which rosemary components block initiation of carcinogenes is by the procarcinogen benzo[a]pyrene (B[a]P) in human bronchial epit helial cells (BEAS-2B). Whole rosemary extract (6 mu g/ml) or an equiv alent concentration of its most potent antioxidant constituents, carno sol or carnosic acid, inhibited DNA adduct formation by 80% after 6 h co-incubation with 1.5 mu M B[a]P. Under similar conditions, cytochrom e P450 (CYP) 1A1 mRNA expression was 50% lower in the presence of rose mary components, and CYP1A1 activity was inhibited 70-90%. The observe d reduction of DNA adduct formation by rosemary components may mostly result from the inhibition of the activation of benzo[a]pyrene to its ultimate metabolites. Carnosol also affected expression of the phase I I enzyme glutathione-S-transferase which is known to detoxify the prox imate carcinogenic metabolite of B[a]P. Treatment of BEAS-2B cells wit h carnosol (1 mu g/ml) for 24 h resulted in a 3- to 4-fold induction o f GST pi mRNA. Moreover, expression of a second important phase II enz yme, NAD(P)H: quinone reductase, was induced by carnosol in parallel w ith GST pi. Therefore, rosemary components have the potential to decre ase activation and increase detoxification of an important human carci nogen, identifying them as promising candidates for chemopreventive pr ograms.