title: Silver nanoparticles exhibit size-dependent differential toxicity and induce expression of syncytin-1 in FA-AML1 and MOLT-4 leukaemia cell lines.
abstract: Human endogenous retrovirus (HERV) sequences make up ~8% of the human genome and increased expression of some HERV proteins has been observed in various pathologies including leukaemia and multiple sclerosis. However, little is known about the function of these HERV proteins or environmental factors which regulate their expression. Silver nanoparticles (AgNPs) are used very extensively as antimicrobials and antivirals in numerous consumer products although their effect on the expression of HERV gene products is unknown. Cell proliferation and cell toxicity assays were carried out on human acute T lymphoblastic leukaemia (MOLT-4) and Fanconi anaemia associated acute myeloid leukaemia (FA-AML1) cells treated with two different sizes of AgNPs (7nm and 50nm diameter). Reverse-transcriptase polymerase chain reaction and western blotting were then used to the assess expression of HERV-W syncytin-1 mRNA and protein in these cells. FA-AML1 cells were more sensitive overall than MOLT-4 to treatment with the smaller 7nm sized AgNp's being the most toxic in these cells. MOLT-4 cell were more resistant and showed no evidence of differential toxicity to the different sized particles. Syncytin-1 mRNA and protein were induced by both 7 and 50nm AgNPs in both cell types yet with different kinetics. In summary, the observation that AgNPs induce expression of syncytin-1 in FA-AML1 and MOLT-4 cells at doses as little as 5 µg/ml is grounds for concern since this protein is up-regulated in both malignant and neurodegenerative diseases. Considering the widespread use of AgNPs in the environment it is clear that their ability to induce syncytin-1 should be investigated further in other cell types.
authors: Viral Oncology, Institute of Cancer Sciences and.
authors: Sultan
authors: S
authors: Alqahtani
authors: Molecular Epidemiology, Faculty of Medical and Human Sciences, University of Manchester, Oxford Road, Manchester M13 9WL, UK.
authors: Pawika
authors: P
authors: Promtong
authors: Viral Oncology, Institute of Cancer Sciences and.
authors: Anthony W
authors: AW
authors: Oliver
authors: Viral Oncology, Institute of Cancer Sciences and.
authors: Xiaotong T
authors: XT
authors: He
authors: Viral Oncology, Institute of Cancer Sciences and.
authors: Thomas D
authors: TD
authors: Walker
authors: Molecular Epidemiology, Faculty of Medical and Human Sciences, University of Manchester, Oxford Road, Manchester M13 9WL, UK.
authors: Andrew
authors: A
authors: Povey
authors: Viral Oncology, Institute of Cancer Sciences and.
authors: Lynne
authors: L
authors: Hampson
authors: Viral Oncology, Institute of Cancer Sciences and ian.hampson@manchester.ac.uk.
authors: Ian N
authors: IN
authors: Hampson
mesh_terms: D049109:Cell Proliferation; D020077:Endogenous Retroviruses / Q000378:metabolism; D005199:Fanconi Anemia / Q000150:complications; D015973:Gene Expression Regulation, Leukemic; D015686:Gene Products, env / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D015458:Leukemia, T-Cell / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D011257:Pregnancy Proteins / Q000187:drug effects* / Q000235:genetics; D012333:RNA, Messenger; D012834:Silver / Q000494:pharmacology / Q000633:toxicity*; D015854:Up-Regulation
chemical_list: D015686:Gene Products, env; D011257:Pregnancy Proteins; D012333:RNA, Messenger; C405335:syncytin; D012834:Silver