Nitrofurazone-induced DNA damage to tissues of mice.

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.