[Analysis of DNA damage induced by nitrosourea derivatives in rat brain tumor cells using a sequencing procedure]

DNA damages caused by various anticancer nitrosourea compounds such as ACNU and MCNU were studied. Reiterated fragments of 167 and 203 base pairs (bp) were obtained after Hind III and Hae III restriction endonuclease digestion of 9L rat brain tumor DNA. The end-labeled reiterated fragments were reacted with ACNU and MCNU, which resulted in the scission breaks corresponding to the locations of guanine on an extended Maxam-Gilbert sequencing gel. Subsequent piperidine hydrolysis yielded scission products more frequently. These results indicate that nitrosoureas such as ACNU and MCNU generate DNA scission breaks and/or alkali-labile sites preferentially at the position of guanine moieties in rat brain tumor DNA.