The phosphorylation of histones in rat liver undergoing malignant transformation.

The incorporation of inorganic phosphate into H1-histones of rat liver was stimulated after the repeated s.c. administration of diethylnitrosamine. This stimulation was observed as early as after the fifth daily injection of the carcinogen and amounts to approximately 3 times the control value on the 60th day of the experiment. The effect was reversible when the application of the carcinogen was not extended beyond 4 weeks. A correlation was observed between these phenomena and alterations in the morphological structure, although the latter required a higher amount of single doses before the first signs of a forthcoming malignant transformation were seen. There was a difference in distribution of phosphate between the individual phosphorylation sites of the H1 molecule as compared to stimulated phosphate incorporation induced by adenosine cyclic 3':5'-monophosphoric acid or liver regeneration. The stimulated phosphorylation was not due to the inflammatory action of the carcinogen.

Tumor-specific inhibition of DNA synthesis and cell proliferation by a factor from bovine placenta--possible mechanism.

A polypeptide isolated from the maternal part of bovine placentas inhibits significantly the incorporation of thymidine into the DNA of tumor cells. When normal cells are used, this effect is found only to a very limited degree. Surface membrane components have been identified which are enriched on tumor cells and which are responsible for a better binding of the inhibitor to tumor cells than to normal cells. After internalization of the receptor-inhibitor complex, a decrease in the nuclear content of two proteins is observed, which might be a requirement for the inhibition of the DNA synthesis.

Inhibition of tumor cell proliferation by a novel growth regulator from placenta: modulation of membrane phosphorylation and oncogene expression.

The tumor specific inhibition of thymidine uptake by a negative growth regulator isolated from the maternal part of the bovine placenta is in concert with an inhibited expression of ras oncogenes. The results indicate that primary processing is blocked in case of Ha-ras, while a lower transcription rate or a stimulated degradation of mRNA is more likely for N-ras. These reactions are preceded by a specific binding of the inhibitor to tumor cell surface membranes. A modulated phosphate incorporation into some of the surface components is observed as a result of the binding process.

The evaluation of an average nucleotide composition from melting curves.

A new formula has been derived for the calculation of the average G + C content - X of DNAs from different origins using thermal melting data. As compared to existing formulas the new method gives highly accurate results, although being much easier to use than similar equations.

Inhibition of DNA synthesis and oncogene expression in tumor cells by the biological factor DIF.

A regulatory factor isolated from the maternal part of bovine placentas (decidua inhibitory factor, DIF) inhibits the incorporation of thymidine into the DNA of a variety of animal and human tumors. The degree of inhibition is dependent on the concentration of the factor. Results indicate that signal transduction occurs via a Ca2+ mobilizing pathway after specific binding of the inhibitor to tumor cell surface receptors. On of the main consequences of DIF action is the inhibition of c-fos and c-myc expression and/or degradation.

Inhibition of thymidine incorporation into the DNA of normal and neoplastic cells by a factor from bovine maternal placenta: interaction of the inhibitor with cell membranes.

An inhibitor was isolated from the maternal part of bovine placentas which inhibits the incorporation of [3H]thymidine into the DNA of a variety of tumor cells to a significantly higher degree as compared to normal cells. This protein-type component was labeled by reaction with N-succinimidyl[2,3-3H]propionate, and interactions with receptors on cell membranes were investigated. Results indicated that receptors on tumor cell surfaces have higher binding capacities versus the inhibitor than those of normal cells. Moreover, an additional type of receptor was detected on tumor membranes. Obviously one of the reasons for the higher inhibitory capacity of the factor in tumor cells is the better internalization of this component.

Early alterations in rat liver chromatin structure after a single dose of diethylnitrosamine.

In the chromatin of 24-h regenerating rat livers, derivative melting profiles are characterized by a high proportion of transitions above 90 degrees C. After the injection of diethylnitrosamine there is a rapid shift to lower melting temperatures. This is due to a rearrangement of the chromatin to higher amounts of nucleosomal components but possibly also a consequence of chemical modifications and conformational alterations of the DNA. In the nonregenerating liver essentially the same observations can be made, although reactions proceed significantly slower. These results are in good agreement with the observation that carcinogens are more active in tissues stimulated to rapid proliferation as compared to resting tissues.