MOLECULAR ANALYSIS OF ETHYL METHANESULFONATE-INDUCED MUTATIONS AT THEHPRT GENE IN THE ETHYL METHANESULFONATE-SENSITIVE CHINESE-HAMSTER CELL-LINE EM-C-11 AND ITS PARENTAL LINE CHO9

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 tr eatment with ethyl methanesulfonate. Ethyl methanesulfonate-induced mu tational spectra were determined at the hprt locus to investigate whet her the same adducts are responsible for mutation induction in both ce ll lines. The mutational spectra for EM-C11 and CHO9 show an important difference. GC-->AT transitions were found in both cell lines at simi lar frequencies; however, the spectrum of CHO9 contains a class of AT- ->GC transitions, which seems to be replaced by a group of deletions i n 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 re sponsible adduct(s) in CHO9 is bypassed resulting in replication error s, while blocking DNA synthesis in EM-C11 causing the observed increas e in cell death. In surviving EM-C11 cells, DNA strand exchanges might have occurred at the position of stalled replication forks, leading t o gross molecular changes. The adduct probably responsible for the AT- ->GC transitions in CHO9 and the deletions in EM-C11 is 3-ethyladenine .