Fullerene derivatives induce premature senescence: A new toxicity paradigm or novel biomedical applications
- Biosciences Division, Los Alamos National Laboratory, M888, TA 43, HRL-2, Los Alamos, NM 87545 (United States)
- Chemistry Division, Los Alamos National Laboratory, J567, TA 46, Los Alamos, NM 87545 (United States)
- Center for Integrated Nanotechnologies (CINT), Los Alamos National Laboratory, P.O. Box 1663, MS K771, Los Alamos, NM 87545 (United States)
Engineered fullerenes (C{sub 60}) are extensively used for commercial and clinical applications based on their unique physicochemical properties. Such materials have also been recognized as byproducts of many industrial activities. Functionalization of C{sub 60} may significantly influence the nature of its interactions with biological systems, impacting its applications and raising uncertainties about its health effects. In the present study, we compared the bioimpact of two chemically modified fullerene derivatives, hexa carboxyl fullerene adduct (Hexa-C{sub 60}) and tris carboxyl fullerene adduct (tris-C{sub 60}) to pristine fullerene C{sub 60} encapsulated with gamma (gamma)-cyclodextrin C{sub 60} (CD-C{sub 60}), using human cutaneous epithelial cells (HEK) to simulate possible applications and occupational dermal exposure route. We report, for the first time, the discovery of premature senescence as a potential endpoint of nanomaterial elicited biological effects, providing a new paradigm for nanoparticle-induced toxicity in human cells. Moreover, this response appeared to be functionalization specific, in that, only tris-C{sub 60} induced senescence. We investigated key biological responses, such as cellular viability, intracellular ROS generation, cell proliferation and cell cycle responses. Our results indicate that the often observed 'anti-apoptotic' function of fullerene derivatives may be independent of their 'ROS scavenging' role as previously reported. We discovered that the tris-C{sub 60}-induced responses were associated with G{sub 0}/G{sub 1} cell cycle arrest and cellular senescence. On further evaluation of the molecular mechanisms underlying the senescent response, a significant decrease in the expression levels of HERC5 was noted. HERC5 is a ubiquitin ligase of the HERC family and is implicated to be involved in innate immune responses to viral and bacterial infections.
- OSTI ID:
- 21344914
- Journal Information:
- Toxicology and Applied Pharmacology, Vol. 244, Issue 2; Other Information: DOI: 10.1016/j.taap.2009.12.025; PII: S0041-008X(09)00532-8; Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0041-008X
- Country of Publication:
- United States
- Language:
- English
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