Isolation of Chinese hamster cells hyposensitive to ethyl methanesulfonate and their characterization in induction and antagonization of sister-chromatid exchanges

Abstract

To better understand the molecular events involved in the formation of SCEs and mutations, 3 clonal sublines were established from a Chinese hamster cell line, Don D-6, on the basis of hyposensitivity to killing by ethyl methanesulfonate. These sublines, referred to as T80-4, T80-4 and T80-7, exhibited greatly altered karyotypes and altered frequencies of SCEs and mutations. These sublines were also less sensitive to chemical mutagens and ultraviolet irradiations as indicated by reduced frequencies of SCEs. This lower sensitivity was not due to differences in the rate of cell proliferation or to a cellular adaptive response. The rate of chemically- or UV-induced SCEs in these sublines did not always relate to cellular ploidy levels. The recent observation that, under constant experimental conditions, the rate of SCEs is a function of cellular ploidy level was not observed for these sublines. Thus, there appeared to be a modification in the intrinsic process of SCE formation. We reported previously that protein synthesis is essential for the induction of mutation as well as for SCE in Don D-6. However, the ability of cycloheximide (CH) to antagonize EMS-induced SCEs and mutations in the T80-7 subline was much lower than in the parental cells or in other sublines. The cells of this subline might contain a defective protein or a modification of the process for which the protein is required.