Resistant Human Glioma Cells Treated with Differences in DNA Alkylation Products Formed in Sensitive

The distribution of alkylated deoxynucleosides and bases has been determined in the DNA of a sensitive and a resistant human gliomaderived cell line exposed to therapeutic levels of |'"l1|.Y-(2-chloroethyl)/V-nitrosourea in vitro. The resistant cell line is 5-fold less sensitive to the cytotoxic effects of yV-(2-chloroethyl)-Ar-nitrosourea and 8-fold less sensitive to sister chromatid exchange than the sensitive cell line. In comparison with the sensitive cells, DNA from the resistant cells contains much less of the cross-link, l-(3-deoxycytidyl),2-(l-deoxyguanosinyl)ethane. DNA from the resistant cells also contains significantly fewer minor base modifications. The decrease in l-(3-deoxycytidyl),2-(l-deoxyguanosinyl)ethane cross-link formation is probably explained by the higher level of O'-alkyltransferase in the resistant cell line. The lower levels of other DNA modifications could be explained by the presence of higher levels of other DNA repair activities.