Telomere susceptibility to cigarette smoke-induced oxidative damage and chromosomal instability of mouse embryos in vitro.
Cigarette smoke is associated with high risk of lung, cardiovascular, and degenerative diseases, reduced fertility, and possibly the health of newborns. Cigarette smoke contains many components and exerts its genotoxicity in part by generating reactive oxidative stress. Telomeres consist of repeated 'G' rich sequences and associated proteins located at the chromosomal ends that maintain chromosomal integrity. We tested the hypothesis that telomere shortening and dysfunction are implicated in smoke associated oxidative damage and chromosomal instability using early mouse embryos in vitro and short-telomere mouse model. Mouse embryos exposed to smoke components, cigarette smoke condensate (CSC) at the concentration of 0.02 mg/ml continuously or 0.1mg/ml for 20 h, or cadmium at 5-100 microM, exhibited increased oxidative stress and telomere shortening and loss, associated with chromosomal instability, apoptosis, and compromised embryo cleavage and development. Remarkably, reduction of oxidative stress by an antioxidant N-acetyl-L-cysteine (NAC) greatly reduced these toxicities. Notably, cadmium led to more severe oxidative damage and telomere dysfunction, which could be more effectively rescued by antioxidant treatment, than did CSC. Moreover, short telomeres predisposed embryos to smoke component-induced oxidative damage. These data further extend our understanding of mechanisms underlying smoke-induced oxidative damage to include telomere dysfunction and chromosomal instability.
Huang
Junjiu
J
Department of Obstetrics and Gynecology, University of South Florida College of Medicine, Tampa, FL 33612, USA.
Okuka
Maja
M
McLean
Mark
M
Keefe
David L
DL
Liu
Lin
L
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology; D002104:Cadmium / Q000633:toxicity; D043171:Chromosomal Instability / Q000187:drug effects*; D004622:Embryo, Mammalian; D047108:Embryonic Development / Q000187:drug effects*; D017404:In Situ Hybridization, Fluorescence; D020287:In Situ Nick-End Labeling; D066298:In Vitro Techniques; D019216:Metals, Heavy / Q000633:toxicity; D051379:Mice; D008856:Microscopy, Fluorescence; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012906:Smoke / Q000009:adverse effects; D012907:Smoking / Q000009:adverse effects*; D016615:Telomere / Q000187:drug effects*; D014026:Nicotiana / Q000009:adverse effects / Q000737:chemistry
D000975:Antioxidants; D019216:Metals, Heavy; D017382:Reactive Oxygen Species; D012906:Smoke; D002104:Cadmium