Induction of deletion mutations by methoxyacetaldehyde in Chinese hamster ovary (CHO)-AS52 cells.
We have reported previously that methoxyacetaldehyde (MALD), a metabolite of 2-methoxyethanol, induces gpt gene mutations in Chinese hamster ovary (CHO)-AS52 cells but not hprt gene mutations in the standard CHO-K1-BH4 cells. In addition, MALD induces chromosome aberrations in both CHO cell lines. The data presented suggest that MALD induces deletion-type mutations. In this study, we analyzed MALD-induced CHO-AS52 mutants for deletion-type mutations using the nested-polymerase chain reaction (nested-PCR) assay. Spontaneous CHO-AS52 mutants are used as untreated control. Ethylnitrosourea (ENU)-induced CHO-AS52 mutants are used as negative control for multilocus deletions since ENU is a potent inducer of point mutations. The results show that the frequency of MALD-induced mutants containing total deletion of the gpt gene is 42.4% which is 2.3-fold higher than that from spontaneous mutants (18.6%). The frequency of ENU-induced deletion mutation is 3%. The data substantiate our hypothesis that MALD induces major deletion mutations.
D000079:Acetaldehyde / Q000031:analogs & derivatives* / Q000633:toxicity; D000410:Alanine Transaminase / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D006224:Cricetinae; D017931:DNA Primers / Q000235:genetics; D005038:Ethylnitrosourea / Q000633:toxicity; D017353:Gene Deletion; D008969:Molecular Sequence Data; D009153:Mutagens / Q000633:toxicity*; D017354:Point Mutation; D016133:Polymerase Chain Reaction
D017931:DNA Primers; D009153:Mutagens; C049826:2-methoxyacetaldehyde; D000410:Alanine Transaminase; D000079:Acetaldehyde; D005038:Ethylnitrosourea