Study on DNA strand breaks induced by sodium nitroprusside, a nitric oxide donor, in vivo and in vitro.
Nitric oxide (NO) as well as its donors has been shown to generate mutation and DNA damage in in vitro assays. The objective of this study was to identify that DNA single-strand breaks (SSBs) could be elicited by NO, not only in vitro but also in vivo. The alkaline single-cell gel electrophoresis (SCGE) was performed to examine the DNA damage in g12 cells and the cells isolated from the organs of mice exposed to sodium nitroprusside (SNP). A modified method, in which neither collagenase nor trypsin was necessary, was used to prepare the single-cell suspension isolated from organs of mice. Results showed that the exposure of g12 cells to 0.13-0.5 micromol/ml SNP with S9 for 1 h induced a concentration-dependent increase in DNA SSBs in g12 cells. The significant increase in DNA migration and comet frequency has appeared in the cells isolated from the spleen, thymus, and peritoneal macrophages of mice after injecting i.p. SNP in the dosage range of 0.67-6.0 mg/kg b.wt for 1 h. However, no obvious increase in DNA strand breaks was observed in the cells isolated from the liver, kidney, lung, brain and heart obtained from the same treated mice. These results suggested that DNA SSBs could be induced by NO in some cells both in vivo and in vitro. There were organ differences in sensitivity in the mice exposed to NO. Spleen, thymus, and macrophages might be the important targets of NO.
Lin
W
W
Department of Toxicology, Beijing Medical University, Beijing, People's Republic of China. zhouzc@mail.bjmu.edu.cn
Wei
X
X
Xue
H
H
Kelimu
M
M
Tao
R
R
Song
Y
Y
Zhou
Z
Z
D017109:Akathisia, Drug-Induced / Q000209:etiology; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D020552:Comet Assay; D003490:Cyanosis / Q000139:chemically induced; D004247:DNA / Q000187:drug effects* / Q000378:metabolism; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D004417:Dyspnea / Q000139:chemically induced; D008297:Male; D051379:Mice; D008862:Microsomes, Liver; D009128:Muscle Spasticity / Q000139:chemically induced; D020030:Nitric Oxide Donors / Q000633:toxicity*; D009573:Nitrites / Q000378:metabolism; D009599:Nitroprusside / Q000378:metabolism / Q000633:toxicity*; D013575:Syncope / Q000139:chemically induced; D013997:Time Factors; D014202:Tremor / Q000139:chemically induced
D020030:Nitric Oxide Donors; D009573:Nitrites; D009599:Nitroprusside; D004247:DNA