Study on DNA strand breaks induced by sodium nitroprusside, a nitric oxidedonor, 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 iden tify 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 (S CGE) was performed to examine the DNA damage in g12 cells and the cells iso lated from the organs of mice exposed to sodium nitroprusside (SNP). A modi fied method, in which neither collagenase nor trypsin was necessary, was us ed to prepare the single-cell suspension isolated from organs of mice. Resu lts showed that the exposure of g12 cells to 0.13-0.5 mu mol/ml SNP with S9 for 1 h induced a concentration-dependent increase in DNA SSBs in g12 cell s. The significant increase in DNA migration and comet frequency has appear ed in the cells isolated from the spleen, thymus, and peritoneal macrophage s 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 obtaine d from the same treated mice. These results suggested that DNA SSBs could b e induced by NO in some cells both in vivo and in vitro. There were organ d ifferences in sensitivity in the mice exposed to NO. Spleen, thymus, and ma crophages might be the important targets of NO. (C) 2000 Published by Elsev ier Science B.V. All rights reserved.