Studies on ehrlich ascites tumour cells: DNA synthesis, and template activity of chromatin for DNA polymerase.

Chromatin obtained from Ehrlich ascites cells on different days after cell inoculation has been assayed for its template activity with added DNA polymerase I. We have found that the template activity is 2 times higher in 7-8 day cell chromatin than in 4-day chromatin. Studies with added polylysine indicate that this increase reflects an increase in initiation sites rather than in accessibility to the enzyme. We have measured the growth fraction, mitotic index and rate of DNA chain growth in the intact cells. The results show that there is a large decrease in growth fraction with age of tumour, the number of cells dropping out of cycle approximately doubling over the period studied. The overall rate of chain growth decreases in the later stages of growth but in a small proportion of cells there is an increase in rate with fewer replicons involved in DNA synthesis. We suggest that in the ascites cells there is a decrease in level of repair and replicative enzymes with age of tumour; this would account both for the increase in initiation sites in the chromatin DNA, for the decrease in number of cells in cycle and for the overall decreased rate of chain growth.