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: methoxyacetaldehyde (MALD) and methoxyacetic acid (MAA), is not adequately investigated yet. We have shown previously that MALD induced mutation in the bacterial 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. We have conducted a cytogenetic study using both CHO cell lines and human lymphocytes to investigate this phenomenon. Our results show that human lymphocytes treated with 10-30 mM MALD for 1 h or 0.05-0.5 mM MALD for 24 h induced significant dose-dependent increase of sister-chromatid exchanges (SCE) (p < 0.05). It also induced significant dose-dependent increase (p < 0.05) of chromosome aberrations in human lymphocytes (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 parent compound, 2-ME did not induce chromosome aberrations nor SCE unless very high doses of the chemical were used. In conclusion, these results indicate that MALD is clastogenic to different cell types therefore it is potentially carcinogenic. The genotoxic effects of 2-ME in humans will be dependent upon the metabolic capability of individuals to bioactivate 2-ME to MALD.
Chiewchanwit
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Department of Preventive Medicine and Community Health, University of Texas Medical Branch, Galveston 77555-1010.
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D000079:Acetaldehyde / Q000031:analogs & derivatives* / Q000633:toxicity; D000818:Animals; D016466:CHO Cells / Q000187:drug effects; D002869:Chromosome Aberrations; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D005026:Ethylene Glycols / Q000633:toxicity*; D006801:Humans; D016014:Linear Models; D008214:Lymphocytes / Q000187:drug effects; D008940:Mitotic Index; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D012854:Sister Chromatid Exchange
D005026:Ethylene Glycols; D009153:Mutagens; C049826:2-methoxyacetaldehyde; C005219:methyl cellosolve; D000079:Acetaldehyde