Effect of zebularine on histology, lymphoma xenografts, and DNA methylation parameters. (A) Hematoxylin and eosin (H&E)-stained 4-μm section thymus samples. The pathological findings in the thymus of the zebularine-treated mice resemble the structure of the normal thymus. Images were captured with an Olympus Vanox microscope (Olympus, Melville, NY) using a 10 ×/0.35 NA objective. (B) Analysis of global DNA methylation by high-performance capillary electrophoresis (HPCE). The irradiated thymus of the zebularine-treated mice shows DNA hypomethylation compared with the lymphomas appearing in the irradiated mice that only receive PBS. (C) Western blot analysis of DNMT1 protein levels in normal thymus and lymphomas appearing in the irradiated mice that only receive PBS and in irradiated thymus of the zebularine-treated mice. (D) Top panels show female athymic nude mice 16 days after injection of 10⁶ MOLT-4 cells. Note the large tumor on the left, corresponding to a PBS-treated mouse, and the small tumor on the opposite figure, corresponding to zebularine-treated mouse. Tumor detail is shown in millimeters, and weight is shown in milligrams. Bottom panels show effect of zebularine treatment on the in vivo growth of MOLT-4 cells. Tumor size was monitored over time, and size is shown in cubic millimeters. Tumoral weight data at 16 days with PBS- and zebularine-treated MOLT-4 xenografts presented as means ± SD.