Differences in DNA alkylation products formed in sensitive and resistant human glioma cells treated with N-(2-chloroethyl)-N-nitrosourea.
The distribution of alkylated deoxynucleosides and bases has been determined in the DNA of a sensitive and a resistant human glioma-derived cell line exposed to therapeutic levels of [3H]N-(2-chloroethyl)-N-nitrosourea in vitro. The resistant cell line is 5-fold less sensitive to the cytotoxic effects of N-(2-chloroethyl)-N-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, 1-(3-deoxycytidyl),2-(1-deoxyguanosinyl)ethane. DNA from the resistant cells also contains significantly fewer minor base modifications. The decrease in 1-(3-deoxycytidyl),2-(1-deoxyguanosinyl)ethane cross-link formation is probably explained by the higher level of O6-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.
Bodell
W J
WJ
Department of Neurological Surgery, University of California, San Francisco 94143.
Tokuda
K
K
Ludlum
D B
DB
D000478:Alkylation; D004247:DNA / Q000378:metabolism*; D004260:DNA Repair; D004351:Drug Resistance; D005038:Ethylnitrosourea / Q000031:analogs & derivatives* / Q000494:pharmacology; D005910:Glioma / Q000378:metabolism; D006801:Humans; D014407:Tumor Cells, Cultured / Q000187:drug effects
C017139:1-(2-chloroethyl)-1-nitrosourea; D004247:DNA; D005038:Ethylnitrosourea