The objective of this study was to examine the regeneration capacity of the spionid polychaete Marenzelleria viridis from Long Island, New York. In the field,~7% of the worms exhibited regeneration of the anterior end. In the laboratory, worms were ablated at the 10th-50th chaetiger and their regeneration documented. Anterior morphogenesis was similar to that previously reported for spionids, with wound healing, blastema formation, differentiation of segments, and formation of feeding and sensory structures (mouth, palps, nuchal organs) occurring within 14 d. Unlike in some spionids, the segments do not appear to all form simultaneously from the blastema; rather, external differentiation of segments was observed from posterior to anterior on the regenerate. The number of segments replaced was equal to the number ablated for up to 10 segments. A maximum of 17 segments were replaced when 20-30 chaetigers were ablated, and the number replaced decreased to 14 when 40-50 chaetigers were ablated. Survival and normal growth of the worms decreased with more chaetigers ablated; a significantly higher number of worms died or grew abnormally with ≥30 chaetigers ablated, compared to worms with ≤20 chaetigers ablated. Members of M. viridis could be valuable model organisms in the study of the cellular mechanisms involved in regeneration, and further research on regeneration in the field should be completed.Additional key words: marine, northwest Atlantic, Polychaeta, regenerate, sublethal predation Invertebrate Biology 135(4): 357-369.

5-Fluorouracil (FU) is a halogenated nucleobase analog that is widely used in chemotherapy. Here we show that 5-hydroxymethyl-2′-deoxyuridine (hmUdR) synergistically enhances the activity of FU in cell lines derived from solid tumors but not normal tissues. While the cytotoxicity of FU and hmUdR was not directly related to the amount of the modified bases incorporated into cellular DNA, incubation with this combination resulted in dramatic increase in the number of single strand breaks in replicating cancer cells, leading to NAD-depletion as consequence of poly(ADP-ribose) synthesis and S phase arrest. Cell death resulting from the base/nucleoside combination did not occur by apoptosis, autophagy or necroptosis. Instead, the cells die via necrosis as a result of NAD depletion. The FU-related nucleoside analog, 5-fluoro-2′-deoxyuridine, also displayed synergy with hmUdR, whereas hmUdR could not be replaced by 5-hydroxymethyluracil. Among other 5-modified deoxyuridine analogs tested, 5-formyl-2′-deoxyuridine and, to a lesser extent, 5-hydroxy-2′-deoxyuridine, also acted synergistically with FU, whereas 5-hydroxyethyl-2′-deoxyuridine did not. Together, our results have revealed an unexpected synergistic interaction between deoxyuridine analogs and FU in a cancer cell-specific manner, and suggest that these novel base/nucleoside combinations could be developed into improved FU-based chemotherapies.