title: Role of sulforaphane in the anti-initiating mechanism of lung carcinogenesis in vivo by modulating the metabolic activation and detoxification of benzo(a)pyrene.
abstract: Biomarkers are central to the molecular epidemiology approach. Since scientific research progress within this standard, a more complete biological understanding of the specific events underlying the multistage carcinogenesis model is essential. Hence the present investigation was designed to assess the anti-initiating potential of Sulforaphane (SFN) against benzo(a)pyrene [B(a)P] induced lung carcinogenesis in female Swiss Albino Mice by evaluating the activities of xenobiotic markers, and the balance between phase I and phase II carcinogen/drug metabolizing enzymes. We sought to institute whether orally administered SFN reaches the lung tissue and increases functional capacity of detoxification enzymes in this tissue and compare the biochemical changes associated with the initiation of cancer. We demonstrated the inhibitory effects of orally administered sulforaphane on B[a]P-induced aryl hydrocarbon receptor (AHR) activation which subsequently resulted in decreased Phase-I enzyme activities in vivo. The study also highlights that treatment with sulforaphane enhanced the Nuclear factor erythroid 2-related factor 2 (Nrf2) transcription which reflects its nuclear accumulation and DNA binding in mice, together with the induction of phase II enzymes as evident from our results. These modulations by sulforaphane further result in decreased carcinogen-induced stress. By and large, the results suggest an anti-initiating role of sulforaphane in pre- and post-initiation phase of experimentally induced lung carcinogenesis in female Swiss albino mice.
authors.affiliation: Department of Medical Biochemistry, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai-600 113, India. kalpanachelian@gmail.com
authors.forename: D
authors.initials: D
authors.lastname: Kalpana Deepa Priya
authors.forename: R
authors.initials: R
authors.lastname: Gayathri
authors.forename: D
authors.initials: D
authors.lastname: Sakthisekaran
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001564:Benzo(a)pyrene / Q000378:metabolism* / Q000633:toxicity; D001711:Biotransformation / Q000187:drug effects; D005260:Female; D005982:Glutathione Transferase / Q000378:metabolism; D008658:Inactivation, Metabolic; D017879:Isothiocyanates; D008175:Lung Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000235:genetics; D018336:Receptors, Aryl Hydrocarbon / Q000502:physiology; D013454:Sulfoxides; D013861:Thiocyanates / Q000494:pharmacology*
chemical_list: D016588:Anticarcinogenic Agents; D017879:Isothiocyanates; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D018336:Receptors, Aryl Hydrocarbon; D013454:Sulfoxides; D013861:Thiocyanates; D001564:Benzo(a)pyrene; D005982:Glutathione Transferase; C016766:sulforaphane