Rosemary components inhibit benzo[a]pyrene-induced genotoxicity in human bronchial cells.
The commonly used spice and flavouring agent, rosemary, derived from the leaves of the plant Rosmarinus officinalis L., displays antioxidant properties in foods and in biological systems. Moreover, in animal models rosemary components were found to inhibit the initiation and tumour promotion phases of carcinogenesis. In this work, we studied the mechanisms by which rosemary components block initiation of carcinogenesis by the procarcinogen benzo[a]pyrene (B[a]P) in human bronchial epithelial cells (BEAS-2B). Whole rosemary extract (6 micrograms/ml) or an equivalent concentration of its most potent antioxidant constituents, carnosol or carnosic acid, inhibited DNA adduct formation by 80% after 6 h co-incubation with 1.5 muM B[a]P. Under similar conditions, cytochrome P450 (CYP) 1A1 mRNA expression was 50% lower in the presence of rosemary components, and CYP1A1 activity was inhibited 70-90%. The observed 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 II enzyme glutathione-S-transferase which is known to detoxify the proximate carcinogenic metabolite of B[a]P. Treatment of BEAS-2B cells with carnosol (1 microgram/ml) for 24 h resulted in a 3- to 4-fold induction of GST pi mRNA. Moreover, expression of a second important phase II enzyme, NAD(P)H: quinone reductase, was induced by carnosol in parallel with GST pi. Therefore, rosemary components have the potential to decrease activation and increase detoxification of an important human carcinogen, identifying them as promising candidates for chemopreventive programs.
Offord
E A
EA
Nestlé Research Centre, Lausanne, Switzerland.
Macé
K
K
Ruffieux
C
C
Malnoë
A
A
Pfeifer
A M
AM
D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D001564:Benzo(a)pyrene / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D001980:Bronchi / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D001984:Bronchial Neoplasms / Q000139:chemically induced / Q000517:prevention & control; D002273:Carcinogens / Q000633:toxicity*; D002478:Cells, Cultured; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D018736:DNA Adducts / Q000096:biosynthesis* / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004790:Enzyme Induction; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005982:Glutathione Transferase / Q000096:biosynthesis; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics; D019684:Magnoliopsida / Q000737:chemistry; D009153:Mutagens / Q000633:toxicity*; D010936:Plant Extracts / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D065607:Cytochrome P-450 Enzyme Inhibitors; D018736:DNA Adducts; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D009153:Mutagens; D010936:Plant Extracts; D012333:RNA, Messenger; D001564:Benzo(a)pyrene; D003577:Cytochrome P-450 Enzyme System; D005982:Glutathione Transferase