Induction of mutation, sister-chromatid exchanges, and chromosome aberrations by 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5 H)-furanone in Chinese hamster ovary cells

Abstract

The strong bacterial mutagen 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5 H)-furanone (MX) was tested for the induction of mutation at the Na/K ATPase locus to ouabain resistance (Oua R), sister-chromatid exchanges (SCEs), and chromosome aberrations (CAs) in Chinese hamster ovary (CHO) cells without metabolic activation. MX increased the frequency of Oua R mutants in CHO cells when the cells were treated with it in PBS (effective dose range 2–3 μg/ml) or in medium (McCoy's 5A) without serum (effective dose range 20–30 μg/ml). MX also induced SCEs in CHO cells, at 0.19–1.5 μg/ml, exposure in PBS; at 6–24 μg/ml, exposure in medium; and at 3–24 μg/ml, exposure in medium plus 2.5% fetal calf serum. The maximum induction of SCEs was about 1.5–2.5-fold compared with control level, irrespective of exposure conditions (PBS, medium or medium plus serum). The most pronounced genotoxic effect of MX was observed in CAs (100% aberrant cells at the dose level of 4 μg/ml, exposure in PBS) which were mainly of the chromatid type. In general, MX was more toxic to CHO cells treated in PBS compared with exposure in medium of medium plus 2.5% serum.