The Chinese hamster cell line EM-C11 has been shown to be 5 times more sensitive than its parental line CHO9, but not hypermutable, after treatment with ethyl methanesulfonate. Ethyl methanesulfonate-induced mutational spectra were determined at the hprt locus to investigate whether the same adducts are responsible for mutation induction in both cell lines. The mutational spectra for EM-C11 and CHO9 show an important difference. GC→AT transitions were found in both cell lines at similar frequencies; however, the spectrum of CHO9 contains a class of AT→GC transitions, which seems to be replaced by a group of deletions in EM-C11. Since the ethyl methanesulfonate-induced mutation frequency for both lines is the same at equal exposure, it is hypothesized that the lesions leading to AT→GC transitions in CHO9 are responsible for the deletions in EM-C11. This phenomenon might be explained if the responsible adduct(s) in CHO9 is bypassed resulting in replication errors, while blocking DNA synthesis in EM-C11 causing the observed increase in cell death. In surviving EM-C11 cells, DNA strand exchanges might have occurred at the position of stalled replication forks, leading to gross molecular changes. The adduct probably responsible for the AT→GC transitions in CHO9 and the deletions in EM-C11 is 3-ethyladenine.

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This work was supported by Grant KWF.90.04 from the Dutch Cancer Society (the Netherlands) and Grant EV5V-CT91-0012 from the Commission of the European Communities.

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