Interaction of γ-irradiation with two new antineoplastic agents, aziridinylbenzoquinone (AZQ) and 4′-(acridinylamino)methanesulfon-m-anisidide (AMSA), in murine tumors in vivo

Johnson, Randall K.; Wodinsky, I; Swiniarski, J; Meaney, Kathleen F.; Clement, Jacob J.

doi:10.1016/0360-3016(79)90782-x

Cited by 4 publications

(1 citation statement)

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“…To address whether mDpro is defective in apoptosis after DNA damage, we examined the ability of mDpro to induce apoptosis in vitro and in vivo in several hematopoietic tissues after DNA damage. Thus, 4 Gy of g-irradiation and 1 mg/ml of the topoisomerase 2 inhibitor, amsacrine, 20 elicited strictly p53-dependent apoptosis as observed by comparing Annexin-V staining of thymocytes from p53 þ / þ and p53 À/À mice after DNA damage. Thymocytes exposed to the optimized doses of DNAdamaging agents (Figure 2a) showed a sixfold increase in apoptosis above untreated control levels for p53 þ / þ cells with both agents, and in cells from mice heterozygous for wild-type p53 and mDpro (p53 þ /mDpro ).…”

Section: Resultsmentioning

confidence: 99%

p53-mediated apoptosis prevents the accumulation of progenitor B cells and B-cell tumors

et al. 2009

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We propose that the apoptotic function of p53 has an important role in B-cell homeostasis, which is important for the prevention of B-cell lymphomas. We created a mouse model (mDpro) that lacked residues 58-88 of the proline-rich domain of p53. mDpro is defective for apoptosis, but is able to arrest cell-cycle progression in hematopoietic tissues. mDpro develops late-onset B-cell lymphoma, but not the thymic T-cell tumors found in p53-null mice. Interestingly, mDpro lymphomas comprised incorrectly differentiated B cells. B-cell irregularities were also detected in mDpro before tumor onset, in which aged mice showed an increased population of inappropriately differentiated B cells in the bone marrow and spleen. We predict that by keeping B-cell populations in check, p53-dependent apoptosis prevents irregular B cells from eventuating in lymphomas.

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Section: Resultsmentioning

confidence: 99%