Induction of mutations and sister-chromatid exchanges in Chinese hamster ovary cells by ethylating agents

Chinese hamster ovary (CHO) cells were exposed to [3H]ethyl nitrosourea (ENU) or [3H]ethyl methanesulfonate (EMS) and the following DNA ethylation products were quantitated: 3- and 7-ethyladenine, O2-ethylcytosine, 3-, 7- and O6-ethylguanine, O2- and O4-ethyldeoxythymidine and the representative ethylated phosphodiester, deoxythymidylyl (3'-5')ethyl-deoxythymidine. When mutations at the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus induced by these same treatments were compared with the observed ethylation products, mutations were found to correlate best with 3- and O6-ethylguanine. EMS induced approximately twice as many sister-chromatid exchanges (SCEs) as ENU at doses yielding equal mutation frequencies. When SCEs were indirectly compared with DNA ethylation products, 3-ethyladenine and ethylated phosphodiesters related best to SCE formation. Because mutation and SCE induction appear, at least in part, to be related to different DNA adducts, SCE induction by simple ethylating agents may not be a quantitative indicator of potentially mutagenic DNA damage.