Cell kinetic alterations in murine mammary tumors following fasting and refeeding

In the present study, nutritional deprivation was shown to markedly alter the growth and cell kinetics of two widely different experimental tumors, the T-1699 transplantable mammary tumor (TMT) and the C3H HeJ spontaneous mammary tumor (SMT). In vitro techniques were used to determine the thymidine labeling index ([³H]TdR LI), the tumor growth fraction, by the primer available DNA polymerase assay (PDP), and the DNA synthesis time (T_S) following fasting and refeeding. In both systems, fasting resulted in suppression of cell proliferation and significant tumor regression. Refeeding re-established the prefasting growth rates and cell kinetic profiles. The kinetic response to fasting in the TMT involved a generalized lengthening of the cell cycle (T_C), while the timing and magnitude of the response to refeeding appear to be dose dependent. In contrast, the kinetic data from the SMT during fasting was consistent with the presence of a cell cycle block in G₁. Removal of this block by refeeding was prompt and was characterized by tumor cell synchronization and recruitment of non-cycling cells.