The centrosome directs chromosomal migration by a complex process of tubulin-chromatin binding. In this contribution centrosomal abnormalities, including centrosomal amplification, were explored in Chinese Hamster Ovary (CHO) and Normal Human Mammary Epithelial (NHMEC) cells exposed to the antiretroviral drug zidovudine (3'-azido-3'-deoxythymidine, AZT). Centrosomal amplification/fragmentation was observed in both cell types and kinetochore positive micronuclei were found in AZT-exposed CHO cells in correlation with dose. Normal human mammary epithelial cell (NMHEC), strain M99005, previously identified as a strain that incorporates high levels of AZT into DNA (High incorporator, HI), showed greater centrosomal amplification when compared with a second strain, NHMEC M98040, which did not incorporate AZT into DNA (Low incorporator, LI). Additionally, an abnormal tubulin distribution was observed in AZT-exposed HI cells bearing multiple centrosomes. Immunofluorescent staining of human cells with Aurora A, a kinase involved in the maturation of the centrosome, confirmed the induction of centrosomal amplification and revealed multipolar mitotic figures. Flow cytometric studies revealed that cells bearing abnormal numbers of centrosomes and abnormal tubulin distribution had similar S-phase percentages suggesting that cells bearing unbalanced chromosomal segregation could divide. Therefore, AZT induces genomic instability and clastogenicity as well as alterations in proteins involved in centrosomal activation, all of which may contribute to the carcinogenic properties of this compound.

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Purpose Little is known regarding post‐transplant renal function following pediatric pre‐emptive KT. Therefore, this study aims to determine whether there is a difference in 1 year post‐transplant renal function outcomes between pre‐emptive and post‐dialysis KT in pediatric transplant recipients. Methods A retrospective review of patients who underwent kidney transplant at our institution between 2000 and 2015 was performed. Kidney transplant recipients were divided into four groups: pre‐DD, post‐DD, pre‐LD, and post‐LD. The clinical outcomes, measured in eGFR (mL/min/1.73 m2), acute rejection episodes within 1 year, and hospitalization within 1 year were compared to between groups in their respective donor types (pre‐DD vs post‐DD; pre‐LD vs post‐LD). Results The 324 patients were identified (21 pre‐DD, 151 post‐DD, 54 pre‐LD, and 98 post‐LD). Post‐DD group had more females (P = 0.018) and post‐operative complications (P = 0.023), although there was no difference in complications requiring intervention (P = 0.129). Post‐LD patients were more likely to be females (P = 0.017) and those with intrinsic renal (non‐urological/structural) ESRD etiology (P = 0.003). The 1‐year eGFR was similar between pre‐DD and post‐DD groups (70.3 [IQR 53.5‐88.5] vs 74.3 [IQR 62.3‐90.5], P = 0.613), as well as pre‐LD and post‐LD groups (66.6 [IQR 47.8‐73.7] vs 63.9 [IQR 55.0‐77.1], P = 0.600). There were no significant differences in rates of acute rejection episodes or hospitalization within 1 year of transplantation for in LD/DD groups. Conclusion There is no significant difference in renal function at 1 year post‐transplant in pediatric patients receiving pre‐emptive or post‐dialysis kidney transplants.

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