Effect of adriamycin on the cell kinetics of 13762 rat mammary tumors and implications for therapy

Abstract

The unperturbed cell kinetics of 13762 mammary tumors in Fischer 344/CRBL rats were studied by fraction labeled mitoses (FLM) and in vitro methods. The 3H-thymidine (3H-TdR) labeling index (LI) was 32.5% and the volume doubling time was approximately 96 hours 14 days after inoculation. The cell cycle, G1, G2, and DNA synthesis times by computer analysis of the FLM data were 11.5, 3.5, 1.3, and 5.4 respectively. The primer available DNA-dependent DNA polymerase labeling index (69%) was similar to the growth fraction calculated from the FLM data. Estimates of cell kinetic parameters from this tumor model, by in vitro methods, were very similar to those obtained by FLM analysis. The effect of Adriamycin (Adr) on the cell kinetics of 13762 tumors was also studied by monitoring the changes in the 3H-TdR LI, the primer available DNA-dependent DNA polymerase labeling index, and the flux of cells from S to G2 phase by the 3H-TdR and 14C-TdR double-labeling method. The results indicated that cell proliferation was inhibited for at least 3 days after 5 mg/kg of Adr. Recovery of cell proliferation was noted between Days 4 and 7 after treatment. Sequential chemotherapy with cyclophosphamide was most effective when administered to coincide with the proliferative recovery after Adr.