Nuclear Macromolecular Changes in Hepatomas

Summary

A new DNA polymerase (6–8S) was detected and isolated from nuclei of several experimental hepatomas. This new polymerase activity could not be found in normal adult rat tissues. However, it appeared in liver nuclei about 2 weeks after dietary introduction of 3′-methyl-4-dimethylaminobenzene (3′-MDAB), increased considerably with time,and reached a prominent maximum between 30–40 days on the diet. The activity of 6–8S nuclear DNA polymerase of the Morris hepatomas could be directly correlated with their degree of differentiation and growth rates.

Dehistonized chromatin was found to be antigenic, capable of producing tissue-specific antibodies. The changes of immunospecificity of dehistonized chromatin in experimental hepatomas were studied. Administration of 3′-MDBA to Fischer rats produced an early change of the immunospecificity of liver chromatin to a new type, common to many experimental malignancies. The affinity of various hepatoma dehistonized chromatin preparations for the Novikoff hepatoma antiserum approximately paralleled the degree of their differentiation as well as their individual growth rates. The fast growing and poorly differentiated 7777 and 3942A hepatomas were more reactive than the slow growing and better differentiated 7800 and 7787 tumors.

Nuclear phosphoprotein kinase activities and nuclear nonhistone protein phosphorylation patterns were studied in the experimental hepatomas. The kinase activities were several times higher in hepatoma than in normal rat liver. The enzyme activities both in hepatomas and normal liver had similar optimal requirements for pH and Mg concentration. Selective changes in the phosphorylation pattern of chromosomal proteins were observed between the normal liver and experimental hepatomas. Most affected was the area of high molecular weight of nonhistone proteins. Supported by U.S. Public Health Service Grants CA-18668 and by National Cancer Institute Contract N01-CP-65730.