In vitro damage of isolated DNA from two brain tumor cell lines induced by a water-soluble antitumor nitrosourea.
We report the DNA sites damaged by the antitumor drug, nimustine hydrochloride (ACNU), in highly reiterated DNA sequences of rat glioma cells. A reiterated fragment of 370 base pairs (bp), obtained after Hind III restriction endonuclease digestion of rat glioma C6 or 9L cells DNA, was divided into 167 and 203 bp by subsequent Hae III enzyme reaction. The reaction of end-labelled 167 and 203 bp fragments with ACNU resulted in scission breaks corresponding to the locations of guanine. Moreover, ACNU and subsequent piperidine hydrolysis produced more frequent breaks of the phosphodiester bonds at the guanine positions, thus forming alkali-labile sites. These results indicate that the preferred site of DNA strand scission induced by ACNU is at guanine positions.
Fushimi
S
S
Neurosurgical Service, Akita University Hospital, Japan.
Mineura
K
K
Itoh
Y
Y
Kowada
M
M
D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D002460:Cell Line; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000187:drug effects*; D005910:Glioma / Q000188:drug therapy / Q000378:metabolism*; D066298:In Vitro Techniques; D015376:Nimustine; D009607:Nitrosourea Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D012995:Solubility; D014867:Water
D004273:DNA, Neoplasm; D009607:Nitrosourea Compounds; D014867:Water; D015376:Nimustine