Growth characteristics of virus-transformed cells. Maximum population density, inhibition by normal cells, serum requirement, growth in soft agar, and xenogeneic transplantability.

Virus transformants (like cancer cells, cells transformed by X-ray or carcinogens, or those which have transformed spontaneously) exhibit a number of phenotypic changes which are usually associated, and which may be lost concurrently. That association is, however, not invariable. More particularly, the altered characteristics here studied (escape from contact inhibition of growth and susceptibility to inhibition by other cells, decreased serum requirement, and ability to grow in soft agar) do not, in and of themselves, endow the cell with the capacity to produce a tumor, at least as judged by the methods of assay here used. Although the question as to whether the tumorigenicity of virus transformants is causally linked to any of these associated changes cannot be answered definitively, the evidence suggests a close linkage, rather than identity, between the determinants of oncogenicity and the other properties here studied.

Properties of chromosomal proteins of human leukemic cells.

Purified chromatin isolated from lymphocytic cells derived from patients with acute leukemia, or other lymphoproliferative disorders has been compared with chromatin isolated from normal human lymphocytic cells by gel electrophoresis and differential gradient ultracentrifugation. Thermal denaturation studies showed higher Tm values for chromatin from leukemic cells, as compared to that of lymphocytic cells from normal donors or patients with infectious mononucleosis, reflecting the diverse complexity of these chromatins with respect to their varying chemical compositions. There are significant differences in the ratios of DNA:RNA:protein, as well as in the ratios of chromatin-associated histone and non-histone proteins; although chromatin-associated histones were more homogeneous than were the non-histone proteins, as adjudged by amino acid analyses and acrylamide gel electrophoresis. These differences in chromatin structure may relate to the differences in gene expression characteristic of these lymphocytic cells. The chromosomal acidic proteins isolated from the purified chromatin of human leukemic cells greatly stimulated the template activity of the chromatin in in vitro RNA synthesis. The non-histone proteins selectively interact with chromatins and influence the RNA polymerase reactions, indicating that there is selective tissue specificity of non-histone proteins.

Homologies in amino acid composition and structure of histone F2al isolated from human leukaemic cells.

Histones F2al extracted from normal and neoplastic cells possess similar amino acid compositions. Tryptic and chymotryptic peptides of the F2al histones have identical chromato-electrophoretic R(F) values. It is concluded that histones F2al from various sources have similar overall structures. The observed differences in the ratios of in-N-monomethyl- and di-in-N-methyl-lysine in the histones from normal and neoplastic cells may be of significance with respect to gene regulation.