prostaglandin-d2 and Precancerous-Conditions

The in vivo induction mechanism of a preneoplastic marker enzyme, glutathione S-transferase P-form (GST-P), by a number of carcinogens and some noncarcinogens such as anti-oxidants [Proc. Natl. Acad. Sci. U.S.A. 85 (1984) 3964] has remained to be solved. Among the various administration routes tested, GST-P became immunohistochemically demonstrable in the liver centrilobular zone 3 after 24-48h on administration of prostaglandin J2's, 15-deoxy-Delta(12,14)-PGJ2, PGJ2 and Delta(12)-PGJ2 to male rats via the portal vein, whereby the animals had been pretreated with Soya oil intraperitoneally to exhaust fatty acid binding proteins. Unsaturated aldehydes, 4-hydroxynonenal, crotonaldehyde and acrolein, given by the same route induced putatively preneoplastic single cells positive for GST-P. As these lipid peroxidation end products are the substrates as well as inducers of the enzyme, its physiological function could be their detoxication. These results indicate that GST-P expression can be mediated through lipid peroxidation possibly accounting for induction observed with a wide variety of carcinogens. In addition, present method may also be of use as a direct, simple, rapid, and sensitive in vivo test in examination of other biological responses.

Topics: Animals; Biomarkers, Tumor; Carcinogenicity Tests; Carcinogens; Carrier Proteins; Fatty Acid-Binding Protein 7; Fatty Acid-Binding Proteins; Glutathione Transferase; Injections, Intravenous; Lipid Peroxidation; Liver; Liver Neoplasms, Experimental; Male; Neoplasm Proteins; Nerve Tissue Proteins; Portal Vein; Precancerous Conditions; Prostaglandin D2; Rats; Rats, Sprague-Dawley; Soybean Oil

The modifying effects of dietary feeding of zerumbone isolated from Zingiber zerumbet on the development of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) were investigated in male F344 rats. Expression of cyclooxygenase (COX)-2 in colonic mucosa exposed to AOM and/or zerumbone was also assayed. In addition, we assessed the effects of zerumbone on cell proliferation activity of crypts by counting silver-stained nucleolar organizer regions protein (AgNORs) in colonic cryptal cell nuclei. To induce ACF rats were given three weekly subcutaneous injections of AOM (15 mg/kg body weight). They were also fed the experimental diet containing 0.01% or 0.05% zerumbone for 5 weeks, starting one week before the first dosing of AOM. AOM exposure produced 84+/-13 ACF/rat at the end of the study (week 5). Dietary administration of zerumbone caused reduction in the frequency of ACF: 72+/-17 (14% reduction) at a dose of 0.01% and 45+/-18 (46% reduction, p<0.001) at a dose of 0.05%. Feeding of zerumbone significantly reduced expression of COX-2 and prostaglandins in colonic mucosa. Zerumbone feeding significantly lowered the number of AgNORs in colonic crypt cell nuclei. These findings might suggest possible chemopreventive ability of zerumbone, through suppression of COX-2 expression, cell proliferating activity of colonic mucosa, and induction of phase II detoxification enzymes in the development of carcinogen-induced ACF.

Topics: Animals; Anticarcinogenic Agents; Azoxymethane; Cell Division; Colon; Colonic Neoplasms; Cyclooxygenase 2; Diet; Dinoprostone; Dose-Response Relationship, Drug; Glutathione Transferase; Intestinal Mucosa; Isoenzymes; Liver; Male; NAD(P)H Dehydrogenase (Quinone); Nucleolus Organizer Region; Precancerous Conditions; Prostaglandin D2; Prostaglandin-Endoperoxide Synthases; Rats; Rats, Inbred F344; Sesquiterpenes; Silver Staining; Zingiberaceae