title: Organ-specific exposure and response to sulforaphane, a key chemopreventive ingredient in broccoli: implications for cancer prevention.
abstract: Naturally occurring sulforaphane (SF) has been extensively studied for cancer prevention. However, little is known as to which organs may be most affected by this agent, which impedes its further development. In the present study, SF was administered to rats orally either in a single dose or once daily for 7 d. Tissue distribution of SF was measured by a HPLC-based method. Glutathione S-transferase (GST) and NAD(P)H:quinone oxidoreductase 1 (NQO1), two well-known cytoprotective phase 2 enzymes, were measured using biochemical assays to assess tissue response to SF. SF was delivered to different organs in vastly different concentrations. Tissue uptake of SF was the greatest in the stomach, declining rapidly in the descending gastro-intestinal tract. SF was rapidly eliminated through urinary excretion, and urinary concentrations of SF equivalents were 2-4 orders of magnitude higher than those of plasma. Indeed, tissue uptake level of SF in the bladder was second only to that in the stomach. Tissue levels of SF in the colon, prostate and several other organs were very low, compared to those in the bladder and stomach. Moreover, induction levels of GST and NQO1 varied by 3- to 6-fold among the organs of SF-treated rats, though not strictly correlated with tissue exposure to SF. Thus, there is profound organ specificity in tissue exposure and response to dietary SF, suggesting that the potential chemopreventive benefit of dietary SF may differ significantly among organs. These findings may provide a basis for prioritising organs for further chemopreventive study of SF.
authors.affiliation: Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY              14263, USA.
authors.forename: Omkara L
authors.initials: OL
authors.lastname: Veeranki
authors.forename: Arup
authors.initials: A
authors.lastname: Bhattacharya
authors.forename: James R
authors.initials: JR
authors.lastname: Marshall
authors.forename: Yuesheng
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism* / Q000652:urine; D001937:Brassica / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D004790:Enzyme Induction; D005753:Gastric Mucosa / Q000378:metabolism*; D005982:Glutathione Transferase / Q000096:biosynthesis; D017879:Isothiocyanates; D007700:Kinetics; D008297:Male; D050217:Metabolic Detoxication, Phase II; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000096:biosynthesis; D009928:Organ Specificity; D035261:Plant Components, Aerial / Q000737:chemistry*; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344; D013270:Stomach / Q000201:enzymology; D013454:Sulfoxides; D013861:Thiocyanates / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism* / Q000652:urine; D014018:Tissue Distribution; D001743:Urinary Bladder / Q000201:enzymology / Q000378:metabolism*
chemical_list: D016588:Anticarcinogenic Agents; D017879:Isothiocyanates; D013454:Sulfoxides; D013861:Thiocyanates; D016660:NAD(P)H Dehydrogenase (Quinone); C507703:NQO1 protein, rat; D005982:Glutathione Transferase; C016766:sulforaphane