Studies on Screening of Anticancer Agents by Tissue Cultures 1. Screening test using established tumor culture cells and primary tumor culture cells

For the purpose to determine inhibitory effects of Chromonycin A(3) and Mitomycin C of the roliferation of tumor cells we conducted tissue cultures in vitro using next 3 established tumor ells, JTC-11 cells (derived from Ehrlich cancer cells), Hela-S(3) cells, and human thyroid cancer ells, and using primary culture cells from methylcholanthrene induced tumors in the presence f the above two drugs, and obtained the following results. 1. Chromomycin A, shows a marked inhibitory effect on JTC-11 cells in the concentration of 10(-3)γ/ml, but it rather accelerates the proliferation of these cells at low concentrations of 10(-5)γ/ml and 10(-5)γ/ml. 2. As to the effect of Mitomycin C on JTC-11 cells, it acts inhibitorily at the high concentration of 10(-2)γ/ml and 10(-3)γ/ml, but at the concentration of 10(-5)γ/ml, it accelerates the growth of these cancer cells. 3. In the presence of Chromomycin A(3) at the concentration of 10(-3)γ/ml it inhibits markedly the proliferation of Hela-S(3) cells, and even at a low concentration of 10(-5)γ/ml there can be seen no accelerative effect. 4. As to the effect of Chromomycin A(3) on human thyroid cancer cells, at the concentration of 10(-3)γ/ml it shows an inhibitory effects, but at the concentration of 10(-4)γ/ml it reveals a slight accelerative effect on the growth of human thyroid cancer cells. 5. The proliferation of primary culture cells from methylcholanthrene induced tumors are inhibited by addition of 10(-3)γ/ml of Mitomycin C. In the addition of Chromomycin A(3) to the primary culture cells, the growth-inhibitory patterns are considerably different at 3 different primary culture cells. It is interesting that the growth of MC2 primary culture cells is rather markedly inhibited at the addition of 10(-4)γ/ml and 10(-5)γ/ml of Chromomycin A(3) as compared with growth in addition of 10(-3)γ/ml. From these results it seems that the determination of direct effects of these two drugs on the proliferation of tumor cells in tissue culture is technically simple and it would reflect also the effects of the drugs in vivo. On the other hand, there is a possibility that when the drug is administered in a low concentration below its optimal concentration in blood, it rather accelerates the tumor proliferation instead of inhibiting it.