George W Hinkal

Publications (2)17.38 Total impact

• Article: Altered senescence, apoptosis, and DNA damage response in a mutant p53 model of accelerated aging.

  George W Hinkal, Catherine E Gatza, Neha Parikh, Lawrence A Donehower
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  ABSTRACT: The tumor suppressors p16(INK4a) and p53 have been implicated as contributors to age-associated stem cell decline. Key functions of p53 are the induction of cell cycle arrest, senescence, or apoptosis in response to DNA damage. Here, we examine senescence, apoptosis, and DNA damage responses in a mouse accelerated aging model that exhibits increased p53 activity, the p53(+/m) mouse. Aged tissues of p53(+/m) mice display higher percentages of senescent cells (as determined by senescence-associated beta-galactosidase staining and p16(INK4a) and p21 accumulation) compared to aged tissues from p53(+/+) mice. Surprisingly, despite having enhanced p53 activity, p53(+/m) lymphoid tissues exhibit reduced apoptotic activity in response to ionizing radiation compared to p53(+/+) tissues. Ionizing radiation treatment of p53(+/m) tissues also induces higher and prolonged levels of senescence markers p16(INK4a) and p21, suggesting that in p53(+/m) tissues the p53 stress response is enhanced and is shifted away from apoptosis toward senescence. One potential mechanism for accelerated aging in the p53(+/m) mouse is a failure to remove damaged or dysfunctional cells (including stem and progenitor cells) through apoptosis. The increased accumulation of dysfunctional and senescent cells may contribute to reduced tissue regeneration, tissue atrophy, and some of the accelerated aging phenotypes in p53(+/m) mice.
  Mechanisms of ageing and development 05/2009; 130(4):262-71. · 4.18 Impact Factor
• Source

  Available from: rice.edu

  Article: Antibacterial activity of fullerene water suspensions (nC60) is not due to ROS-mediated damage.

  Delina Y Lyon, Lena Brunet, George W Hinkal, Mark R Wiesner, Pedro J J Alvarez
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  ABSTRACT: The cytotoxic and antibacterial properties of nC 60, a buckminsterfullerene water suspension, have been attributed to photocatalytically generated reactive oxygen species (ROS). However, in this work, neither ROS production nor ROS-mediated damage is found in nC 60-exposed bacteria. Furthermore, the colorimetric methods used to evaluate ROS production and damage are confounded by interactions between nC 60 and the reagents, yielding false positives. Instead, we propose that nC 60 exerts ROS-independent oxidative stress, thus reconciling conflicting results in the literature.
  Nano Letters 06/2008; 8(5):1539-43. · 13.20 Impact Factor