CYTOGENETIC EFFECTS OF 2-METHOXYETHANOL AND ITS METABOLITE, METHOXYACETALDEHYDE, IN MAMMALIAN-CELLS IN-VITRO

Glycol ethers such as 2-methoxyethanol (2-ME) are reproductive toxins. The genotoxicity of 2-ME, especially its metabolites: methoxyacetalde hyde (MALD) and methoxyacetic acid (MAA), is not adequately investigat ed yet. We have shown previously that MALD induced mutation in the bac terial gpt gene which is inserted in an autosome of CHO-AS52 cell line but not in the hprt gene on the X chromosome of CHO-K1-BH4 cell line. These data suggest that MALD induces major deletion-type mutation. If this prediction is correct we would expect to observe that MALD is an efficient inducer of chromosome aberrations in both CHO cell lines. W e have conducted a cytogenetic study using both CHO cell lines and hum an lymphocytes to investigate this phenomenon. Our results show that h uman lymphocytes treated with 10-30 mM MALD for 1 h or 0.05-0.5 mM MAL D for 24 h induced significant dose-dependent increase of sister-chrom atid exchanges (SCE) (p < 0.05). It also induced significant dose-depe ndent increase (p < 0.05) of chromosome aberrations in human lymphocyt es (10-40 mM treated for 1 h, or 0.05-2.5 mM for 24 h) and in both CHO cell lines (1.25-20 mM for 3 h). Treatment of these cells with the pa rent compound, 2-ME did not induce chromosome aberrations nor SCE unle ss very high doses of the chemical were used. In conclusion, these res ults indicate that MALD is clastogenic to different cell types therefo re it is potentially carcinogenic. The genotoxic effects of 2-ME in hu mans will be dependent upon the metabolic capability of individuals to bioactivate 2-ME to MALD.