A Preliminary Report on the Thymidine Labeling Indices and Kinetics of Cell Proliferation in Selected Morris Hepatomas

Abstract

SUMMARY.-The 1 hour thymidine labeling indices have been determined for 8 hepatomas which have growth rates which vary by a factor of 14. The indices for these tumors vary only by a factor of 4. Little correlation was found. Preliminary results have been obtained on the kinetics of cell proliferation of the rapidly growing Hepatoma H-35tc2. The tumor transfer time is 07 months and the growth rate is 7*0 cm. per month. The calculated values for times in different phases of the cell cycle for H-35tc2, assuming a log normal distribution for phase duration, were as follows: Tgl (Gap I)-11.0 hours; T. (DNA synthetic period)-6-6 hours; Tg2 (Gap II)-4*2 hours; Tm (mitotic time)-0.4 hours. Therefore, the total time, Tc, for one cell cycle was calculated to be 22*2 hours.The potential doubling time was calculated to be 43 hours. The GF (growth fraction) was estimated to be 53 per cent which would suggest that approximately one-half the total cell population is nonproliferating.THE availability of a large series of chemically induced hepatomas has permitted a rather broad investigation of the problem of neoplastic transformation. One of the authors (H.P.M.) has made available to numerous investigators some 35 different tumor lines which have more than a 20-fold difference in growth rate as well as marked differences in the frequency and magnitude of genetic, metabolic, and morphological deviations (Morris, 1965).Preliminary studies have been made on the relative rates of incorporation of tritium labeled thymidine into nuclear DNA by 4 of these hepatoma lines which have considerable differences in growth rates (Looney and Mayo, 1969;Chang, Morris and Looney, 1968). It might be expected that the thymidine labeling index for the faster growing tumors would be greater than for the slower growing tumors. However, the 1 hour thymidine labeling indices for the 4 hepatomas were found to be similar even though the growth rates (tumor transfer times) vary by a factor of 4.For this reason, we have initiated studies of the kinetics of cell proliferation and cell loss in these tumors, in the hope that an understanding of these processes will allow us to better utilize radiation and chemotherapeutic agents in the clinical management of neoplastic disease. Changes in the approach to the treatment of cancer could occur as a result ofour more precise understanding ofhow tumors grow.