Enhancement of chemosensitivity of quiescent cell populations in murine solid tumors using nicotinamide

Abstract

Cis-diamminedichloroplatinum(II) (CDDP) was intraperitoneally injected into mice bearing SCC VII or EMT6/KU tumors after 10 administrations of 5-bromo-2'-deoxyuridine (BUdR) to label all the proliferating tumor cells. One hour later, the tumors were excised, minced and trypsinized. The tumor cell suspensions were incubated with cytochalasin B (a cytokinesis blocker). The micronucleus (MN) frequency was determined using immunofluorescence staining to BUdR. The cells that were not labeled with BUdR could be regarded as the quiescent cells. The MN frequency in total tumor cells was determined from the tumors that were not pretreated with BUdR. To modify the sensitivity to CDDP, nicotinamide was intraperitoneally injected before CDDP administration. In both tumor system, the MN frequency in quiescent cells was lower than in total cells. Nicotinamide pretreatment increased the MN frequency in total and quiescent cells in both tumor systems, especially in total cells of the SCC VII tumor. The nicotinamide injection increased the uptake of 195mPt-CDDP into the total cells, especially in the SCC VII tumor. Nicotinamide administration before chemotherapy using CDDP was considered to be effective for tumor control, especially in tumors including large acutely hypoxic fractions such as the SCC VII murine tumor.