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The majority of hematopoietic stem cells (HSCs) are maintained in a quiescent state to minimize premature exhaustion induced by various stresses. However, quiescent HSCs are vulnerable to mutagenesis because of attenuated DNA repair and DNA damage response programs. Basal abundant expression of prosurvival BCL-2 proteins further endows HSCs with high resistance to apoptosis. In contrast, HSCs elicit strong activation of p53 upon DNA damage, resulting in enhanced activation of proapoptotic BCL-2 signals through p53. ASPP1, an apoptosis-stimulating protein of p53, is highly expressed in HSCs and preserves HSC pool integrity via selective induction of apoptosis. In this paper, we discuss the role of p53 and mitochondrial apoptosis in HSC regulation and introduce the current understanding of how p53 activity is regulated to achieve a good balance between maintaining the HSC pool and preventing hematological malignancies. [ABSTRACT FROM AUTHOR]

Aminoguanidine (AG), a prototype therapeutic dicarbonyl scavenger, is the most potent drug available today to inhibit the formation of advanced glycation endproducts (AGEs) and to reverse glycation-mediated damage in normal aging. This paper examines the ability of AG to cause damage to supercoiled plasmid DNA in the presence of the transition metal, Fe+3. Damage to DNA was dependent on the concentrations of both the transition metal and AG. We could detect hydroxyl radical as well as hydrogen peroxide during the incubation of AG with Fe+3. Thus this finding further cautions against the indiscriminate use of AG in clinical prophylaxis in diabetes and questions its use as a therapeutic agent. [ABSTRACT FROM AUTHOR]

Although p53 is clearly involved in the salvage pathway to DNA damage, its frequent mutations do not explain the efficacy of radiotherapy and chemotherapy. Indeed, around 50% of all human cancers show mutations in p53, and a further fraction show a functional inactivation of the protein. Nevertheless, patients seem to respond to therapy that would otherwise require a functional p53. At least in part, these responses could be explained by the path way mediated by p73. This mechanism is parallel to, but independent of the p53 pathway. Several pieces of evidence show a significant interaction between these two proteins. Therefore, while p53 can be rightly defined as the guardian of the genome, we could think of p73 as the "assistant" guardian of the genome! [ABSTRACT FROM AUTHOR]