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 μg/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 μM 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 μg/ml) for 24 h resulted in a 3- to 4-fold induction of GSTπ mRNA. Moreover, expression of a second important phase II enzyme, NAD(P)H: quinone reductase, was induced by carnosol in parallel with GSTπ. 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.
Cigarette smoking is causally associated with a large number of human cancers ( 1). Tobacco use is by far the most widespread link between exposure to known carcinogens and death from cancer and is therefore a model for understanding mechanisms of cancer induction. Benzo(a)pyrene (BP) is a highly carcinogenic polycyclic aromatic hydrocarbon (PAH) present in emission exhausts, in charbroiled food, and in small quantity of cigarette smoke ( 2– 5), typically <10 ng/cigarette ( 6). BP is 1 of >60 carcinogens in cigarette smoke that is involved in the etiology of lung cancer ( 7). It is metabolically activated into BP-7,8-diol-9,10-epoxide (BPDE), which reacts with DNA predominantly at the N2 position of guanine to produce primarily N2-guanine lesions [e.g., BPDE-N2-deoxyguanosine (BPDE-dG) adduct; ref. 8]. The presence of BPDE-DNA adducts in human tissues has been conclusively established ( 9) and BPDE-dG adduct concentrated exclusively in bronchial cells and thus implicated in the initiation of human lung cancer ( 10). Although considerable evidence implicates BP as important causative agent of smoking-related cancers, its role is clearly not exclusive.
This carcinogen is metabolized by phase I enzymes to a large number of metabolites, including phenols, arene oxides, quinones, dihydrodiols, and diol epoxides ( 11). An overview of BP metabolic way leading to the formation of (+)-anti-BPDE-dG adduct is presented in Fig. 1
Principal metabolic pathway and DNA binding of the carcinogen BP. BP is a tobacco carcinogen that may be converted in vivo enzymatically or by oxygen reactive species to yield DNA-reactive dihydrodiol epoxides. Stereoselective generation of the mutagenic (+)-anti-BPDE from (−)-BP-7,8-dihydrodiol is catalyzed by CYP-dependent monooxygenases (P450) or ROS. Subsequent reaction of this electrophilic intermediate with genomic DNA produces stable adduct between dihydrodiol epoxide and the exocyclic amino group of guanosine. This kind of DNA lesion may be converted into mutations within the following replication cycle unless repair of this adduct is produced.
Check complete article at http://cancerres.aacrjournals.org/content/66/24/11938
Published 15 December 2006 at Cancer Research Journal
American Association of Cancer Research
Knowing Grilling or Barbecuing generates Benzopyrenes you can use this article to understand the real issues found when you eat grilled food cooked under the traditional/conventional methods including Card-Broilers.
There is no sentence “there is no evidence”. knowing Benzopyrenes are related with cancer diseases and Grilling/Barbecuing also produce them it’s not difficult to associate.