Lipid peroxidation end products-responded induction of a preneoplastic marker enzyme glutathione S-transferase P-form (GST-P) in rat liver on admistration via the portal vein.
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.
Satoh
K
K
Second Department of Biochemistry, School of Medicine, Hirosaki University, 5 Zaifu-cho, 036-8562, Hirosaki, Japan. kisatoh@mail.cc.hirosaki-u.ac.jp
Hayakari
M
M
Ookawa
K
K
Satou
M
M
Aizawa
S
S
Tanaka
M
M
Hatayama
I
I
Tsuchida
S
S
Uchida
K
K
D000818:Animals; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D015197:Carcinogenicity Tests / Q000379:methods; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity*; D002352:Carrier Proteins / Q000378:metabolism; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005982:Glutathione Transferase / Q000096:biosynthesis*; D007275:Injections, Intravenous; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental / Q000378:metabolism; D008297:Male; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D011169:Portal Vein; D011230:Precancerous Conditions / Q000378:metabolism; D015230:Prostaglandin D2 / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013024:Soybean Oil / Q000008:administration & dosage
D014408:Biomarkers, Tumor; D002273:Carcinogens; D002352:Carrier Proteins; C490174:Fabp7 protein, rat; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; C037112:9-deoxy-delta-9-prostaglandin D2; D013024:Soybean Oil; D005982:Glutathione Transferase; D015230:Prostaglandin D2