Decreased connexin32 and a characteristic enzyme phenotype in clofibrate-induced preneoplastic lesions not shared with spontaneously occurring lesions in the rat liver.

Autor: Tsuda, Hiroyuki, Asamoto, Makoto, Iwahori, Yoshio, Hori, Takaaki, Ota, Tomonori, Baba-Toriyama, Hiroyasu, Uehara, Nobuaki, Kim, Dae Joong, Krutovskikh, Vladimir A., Takasuka, Nobuo, Tsuchiya, Takayuki, Mutai, Mamoru, Tatematsu, Masae, Yamasaki, Hiroshi
Zdroj: Carcinogenesis; 1996, Vol. 17 Issue 11, p2441-2448, 8p
Abstrakt: Two different types of focal preneoplastic lesions, tentatively named Type I and II lesions, were recognized in the liver of rats chronically treated with clofibrate for 104 weeks. Type I lesions were characterized by mostly negative glucose-6-phosphate dehydrogenase (G6PD) activity (6 out of 10, 60%) and positive expression of succinate dehydrogenase (10 out of 10, 100%), in addition to the previously documented complete lack of expression of glutathione S-transferase, placental form (GST-P) and γ-glutamyl trans-peptidase (GGT). Furthermore, most importantly, Type I lesions exhibited a clear decrease in immunohistochemically demonstrated connexin32 (Cx32) spot counts on their hepatocyte membranes, similarly to nitrosamine-induced lesions. In contrast, Type II lesions, mostly small in size and positively expressing GST-P and/or GGT and G6PD, similarly to their previously reported nitrosamine-induced counterparts, did not exhibit a significant decrease in Cx32 count. In addition, spontaneously occurring lesions, again sharing the same enzyme phenotype, did not show a decrease in Cx32. The results indicate that: (i) a clear distinction between the two lesions, with Type I being involved in clofibrate-induced tumors and Type II being more likely to be spontaneous in nature; (ii) a decrease in Cx32 is closely linked to lesion development and possibly stage of progression, irrespective of the enzyme phenotype and the applied carcinogen; (iii) the unaltered condition of Cx32 may suggest a slow growing or non-progressive nature. [ABSTRACT FROM PUBLISHER]
Databáze: Complementary Index