Correlation between formamidopyrimidine DNA glycosylase (Fpg)-sensitive sites determined by a comet assay, increased MDA, and decreased glutathione during long exposure to thinner inhalation.
Thinner inhalation causes toxic effects in a variety of organs, principally in the central nervous system. Some studies have shown oxidative stress effects of thinner inhalation, such as: activation of free radical processes, decrease of antioxidants, and oxidation products of proteins and lipids but not of DNA. The aim of this study is to investigate the effect of thinner inhalation on DNA. We used the comet assay in conjunction with the enzyme formamidopyrimidine glycoslyase (Fpg). Our results show a significant increase in Fpg-sensitive sites in DNA of lymphocytes from rats exposed to thinner fumes compared to lymphocytes from control rats (p < 0.05). Moreover, DNA damage detected with Fpg shows a high correlation with increased malondialdehyde (MDA) and decreased glutathione (GSH), two widely used biomarkers of oxidative stress. The most abundant base oxidation product found in DNA is 8-oxoguanine; it is the main substrate of Fpg and the most commonly used biomarker for oxidative DNA damage. This suggests that oxidative DNA damage is at least partly responsible for the DNA damage detected by Fpg. We propose the comet assay in combination with Fpg as a sensitive biomarker to monitor exposure to thinner inhalation. Limitations of this method are discussed.
Martínez-Alfaro
M
M
Departamento de Neurobiología del Desarrollo y Neurofisiología, Instituto de Neurobiología, Campus UNAM-Juriquilla, Apdo, Postal 1-1141, Querétaro 76001, México. martinea@inb.unam.mx
Palma-Tirado
L
L
Sandoval-Zapata
F
F
Cárabez-Trejo
A
A
D000280:Administration, Inhalation; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D020552:Comet Assay; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D004249:DNA Damage / Q000502:physiology*; D043382:DNA-Formamidopyrimidine Glycosylase / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism*; D009930:Organic Chemicals / Q000008:administration & dosage / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012997:Solvents / Q000008:administration & dosage / Q000633:toxicity*; D018709:Statistics, Nonparametric
D009930:Organic Chemicals; D012997:Solvents; D008315:Malondialdehyde; D004247:DNA; D043382:DNA-Formamidopyrimidine Glycosylase; D005978:Glutathione