Olive P L
Chem Biol Interact. 1978 Mar;20(3):323-31. doi: 10.1016/0009-2797(78)90110-2.
Cytotoxicity and DNA damage by nitrofurans has previously been correlated with metabolic reduction of these drugs in vitro. In the present study, nitrofurazone increased the rate of disappearance of stable [3H]thymidine labelled DNA from tissues of mice fed 0.1% nitrofurazone in the diet. Significant loss of labelled DNA occurred within 25 days after the start of the diet in all tissue observed, and loss was in relation to the rate of metabolic reduction of nitrofurazone. A similar correlation was found when another endpoint for DNA damage was used; nitrofurazone reduced by mouse tissue slices caused DNA single-strand breaks in cultured mouse L cells incubated in vitro with the tissues. Again, the ability of each tissue to produce toxic nitrofurazone metabolites determined the amount of DNA damage to the L cells.
呋喃类药物的细胞毒性和DNA损伤此前已与这些药物在体外的代谢还原相关联。在本研究中，呋喃西林提高了喂食含0.1%呋喃西林饮食的小鼠组织中稳定的[3H]胸腺嘧啶标记DNA的消失速率。在观察的所有组织中，喂食开始后25天内出现了标记DNA的显著损失，且损失与呋喃西林的代谢还原速率相关。当使用另一个DNA损伤终点时也发现了类似的相关性；小鼠组织切片还原的呋喃西林在体外与组织一起孵育的培养小鼠L细胞中导致了DNA单链断裂。同样，每个组织产生有毒呋喃西林代谢物的能力决定了对L细胞的DNA损伤量。
