Role of air pollution Particulate Matter (PM(2.5)) in the occurrence of loss of heterozygosity in multiple critical regions of 3p chromosome in human epithelial lung cells (L132).
Lung cancer still remains the most frequent type of cancer all around the world and the leading cause of cancer-related death. Even if tobacco use takes a major part in etiology of lung cancer, other explanations like genetic and lifestyle factors, and occupational and/or environmental exposure to carcinogens have to be considered. Hence, in this study, we were interested in the ability of in vitro short-term exposure to air pollution Particulate Matter (PM) to induce genomic alterations in Dunkerque City's PM(2.5)-exposed human epithelial lung cells (L132). The occurrence of MicroSatellite (MS) alterations in 3p multiple critical regions (i.e. 3p14.1, 3p14.2, 3p14.3, 3p21.1, 3p21.31, and 3p21.32) identified as showing frequent allelic losses in benign or malignant lung diseases, was also studied in Dunkerque City's PM(2.5)-exposed L132 cells. Negative (i.e. TiO(2); desorbed PM, dPM), and positive (i.e. benzo[a]pyrene, B[a]P) controls were also included in the experimental design. Loss Of Heterozygosity (LOH) and/or MicroSatellite Instability (MSI) were reported 72h after L132 cell exposure to dPM (i.e. 61.71microg dPM/mL or 12.34microgdPM/cm(2)), PM (i.e. 75.36microgPM/mL or 15.07microgPM/cm(2)), or B[a]P (i.e. 1microM). In agreement with the current literature, such MS alterations might rely on the ability of dPM, PM or B[a]P to induce oxidative stress conditions, thereby altering DNA polymerase enzymes, enhancing DNA recombination rates, and inhibiting DNA repair enzymes. Hence, we concluded that the occurrence of dramatic MS alterations in 3p chromosome multiple critical regions could be a crucial underlying mechanism, which proceeded the lung toxicity in air pollution PM-exposed target L132 cells.
Service de Pneumologie, Hôpital Saint-Philibert, Groupement Hospitalier de l'Institut Catholique-Faculté Libre de Médecine de Lille, Rue du Grand But, BP 249, 59462 Lomme Cedex, France.
Françoise
F
Saint-Georges
Guillaume
G
Garçon
Fabienne
F
Escande
Imane
I
Abbas
Anthony
A
Verdin
Pierre
P
Gosset
Philippe
P
Mulliez
Pirouz
P
Shirali
D002460:Cell Line; D002893:Chromosomes, Human, Pair 3 / Q000187:drug effects*; D004247:DNA / Q000737:chemistry / Q000187:drug effects / Q000235:genetics; D004847:Epithelial Cells / Q000187:drug effects; D006801:Humans; D019656:Loss of Heterozygosity / Q000187:drug effects*; D008168:Lung / Q000187:drug effects* / Q000648:ultrastructure; D008171:Lung Diseases / Q000139:chemically induced* / Q000235:genetics; D018895:Microsatellite Repeats / Q000187:drug effects; D010316:Particle Size; D052638:Particulate Matter / Q000633:toxicity*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000187:drug effects
D052638:Particulate Matter; D004247:DNA