ENHANCEMENT OF CHEMOSENSITIVITY OF QUIESCENT CELL-POPULATIONS IN MURINE SOLID TUMORS USING NICOTINAMIDE

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 trypsinize d. The tumor cell suspensions were incubated with cytochalasin B (a cy tokinesis blocker). The micronucleus (MN) frequency was determined usi ng immunofluorescence staining to BUdR. The cells that were not labele d with BUdR could be regarded as the quiescent cells. The MN frequency in total tumor cells was determined from the tumors that were not pre treated 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 ce lls. Nicotinamide pretreatment increased the MN frequency in total and quiescent cells in both tumor systems, especially in total cells of t he SCC VII tumor. The nicotinamide injection increased the uptake of P t-195m-CDDP into the total cells, especially in the SCC VII tumor. Nic otinamide administration before chemotherapy using CDDP was considered to be effective for tumor control, especially in tumors including lar ge acutely hypoxic fractions such as the SCC VII murine tumor.