Effect of DNA hypomethylation on genotoxicity and apoptogenicity of sodium arsenite in laboratory mice.
The present study aims to evaluate the effect of DNA hypomethylation state on genotoxicity and apoptogenicity induced by sodium arsenite (NaAsO2) in normal adult male SWR/J mouse bone marrow cells. Animals were treated with intraperitoneally (i.p.) injected with (2.25, 4.50 or 9 mg kg(-1) b.wt. of NaAsO2 which represent 0.25, 0.50 or 1 of LD5, respectively) and killed 24 h later. Another different group of male mice was treated with three doses of 5-Azacitidine (5-AzaC), 5 mg kg(-1) b.wt. each dose and 3 h intervals between them. NaAsO2 administered after 6 days of the last dose. The three single doses of sodium arsenite alone significantly (p<0.05) increased the rate of total structural Chromosomal Aberrations (CAs), rate of Sister Chromatid Exchanges (SCEs), micronucleus (MNs) formation, PARP and Lamia-A degradation and apoptosis as compared with the negative control. The combined treatment with hypomethylation agent 5-AzaC significantly increased the rate of SCEs induced by NaAsO2 at low dose. Moreover, this treatment significantly increased the rate of polyploidy at all combined used doses. Furthermore, this treatment induced apoptosis at all used doses. The present study has shown that DNA hypomethylation had a negative effects represented in rate of (CAs), polyploidy, PARP degradation and apoptosis induced by (NaAsO2). On the other hand, DNA hypomethylation had positive effects represented in decreas rate of pulverized chromosomes, centromeric attenuations, (SCEs), (MNs) formation, prevent Lamina-A degradation and apoptosis.
Alarifi
Saud A
SA
Department of Zoology, Science College, King Saud University, Riyadh, Saudi Arabia.
Alkahtani
Saad
S
Tarboush
F M Abou
FM
Al-Qahtani
Ahmed
A
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D018053:Arsenites / Q000633:toxicity*; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000502:physiology; D002869:Chromosome Aberrations; D019175:DNA Methylation; D004791:Enzyme Inhibitors / Q000633:toxicity; D006801:Humans; D034904:Lamin Type A / Q000378:metabolism; D008297:Male; D051379:Mice; D015162:Micronucleus Tests; D009153:Mutagens; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D012854:Sister Chromatid Exchange / Q000187:drug effects; D017670:Sodium Compounds / Q000633:toxicity*
D018053:Arsenites; D004791:Enzyme Inhibitors; D034904:Lamin Type A; D009153:Mutagens; D017670:Sodium Compounds; C017947:sodium arsenite; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases