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Title: Molecular analysis of ethyl methanesulfonate-induced mutations at the hprt gene in the ethyl methanesulfonate-sensitive Chinese hamster cell line EM-C11 and its parental line CHO9. Author: Op het Veld CW, Zdzienicka MZ, Vrieling H, Lohman PH, van Zeeland AA. Journal: Cancer Res; 1994 Jun 01; 54(11):3001-6. PubMed ID: 8187089. Abstract: 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.[Abstract] [Full Text] [Related] [New Search]