DECREASED CONNEXIN32 AND A CHARACTERISTIC ENZYME PHENOTYPE IN CLOFIBRATE-INDUCED PRENEOPLASTIC LESIONS NOT SHARED WITH SPONTANEOUSLY OCCURRING LESIONS IN THE RAT-LIVER

Two different types of focal preneoplastic lesions, tentatively named Type I and II lesions, were recognized in the liver of rats chronicall y treated with clofibrate for 104 weeks, Type I lesions were character ized by mostly negative glucose-6-phosphate dehydrogenase (G6PD) activ ity (6 out of 10, 60%) and positive expression of succinate dehydrogen ase (10 out of 10, 100%), in addition to the previously documented com plete lack of expression of glutathione S-transferase, placental form (GST-P) and gamma-glutamyl transpeptidase (GGT), Furthermore, most imp ortantly, Type I lesions exhibited a clear decrease in immunohistochem ically 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-in duced counterparts, did not exhibit a significant decrease in Cx32 cou nt. In addition, spontaneously occurring lesions, again sharing the sa me enzyme phenotype, did not show a decrease in Cx32, The results indi cate that: (i) a clear distinction between the two lesions, with Type I being involved in clofibrate-induced tumors and Type II being more l ikely to be spontaneous in nature; (ii) a decrease in Cx32 is closely linked to lesion development and possibly stage of progression, irresp ective of the enzyme phenotype and the applied carcinogen; (iii) the u naltered condition of Cx32 may suggest a slow growing or non-progressi ve nature.