Alterations of ornithine decarboxylase gene during the progression of rat liver carcinogenesis.

Abstract

Liver nodules and carcinomas, developing in F344 rats initiated with diethylnitrosamine, exhibit high ornithine decarboxylase (ODC) activity and DNA synthesis. ODC-related RNAs of 1.8, 2.1 and 2.6 kb are produced by normal rat liver. Early preneoplastic nodules, developing 10 weeks after initiation, showed overproduction of 1.8 and 2.1 kb RNAs, while the 2.6 kb RNA was barely detectable. Rises in the 1.8, 2.1 and 2.6 kb RNAs occur in late nodules (30 weeks after initiation) and in carcinomas. The comparison of different tissues for relative increase in ODC activity, RNA levels and DNA synthesis showed that these parameters behaved in the same way: highest increases occurred in early nodules and carcinomas. These observations suggest that overexpression of ODC gene and alterations in regulatory mechanisms of ODC gene expression may be implicated in the progression of preneoplastic lesions to malignancy. Southern blot analysis of PstI DNA digests revealed the presence of ODC gene rearrangement in two carcinomas and in one late nodule. However, the role of this phenomenon in the progression of preneoplastic lesions is unclear, due to the possibility that ODC pseudogenes are involved instead of or in addition to ODC gene.