REDUCED TAMOXIFEN ACCUMULATION IS NOT ASSOCIATED WITH STIMULATED GROWTH IN TAMOXIFEN RESISTANCE

To study tamoxifen resistance-stimulated growth, 30 female ovariectomi zed nude mice were implanted with tamoxifen-resistant tumors and treat ed with 10-1000 mu g/day of tamoxifen citrate subcutaneously. Tamoxife n stimulated MCF-7 tumor growth in a dose-dependent manner, with tumor al tamoxifen concentrations increasing proportionally to the dose (1-1 3 nmol/g), as measured by high-performance liquid chromatography (HPLC ). Flow-cytometric analysis revealed that tamoxifen-resistant tumors h ad a different DNA content as compared with wild-type MCF-7 cells. In contrast to earlier results, these data suggest that tamoxifen resista nce-stimulated growth is associated with increasing rather than decrea sing tumoral tamoxifen concentrations. Furthermore, the observed ploid y changes in the tamoxifen-resistant tumors imply that a genetic basis may exist for the development of tamoxifen resistance.