Concurrent teratogenic and mutagenic action of 2-methoxyethanol in Drosophila melanogaster larvae resulted in similar phenotypes: close resemblance to directed mutations.
Early third instar larvae of wild-type Drosophila melanogaster were transferred to medium supplemented with 2-methoxyethanol (2-ME) or ethylene glycol monomethyl ether. 2-ME produced terata in adult flies as wing notches and duplications of macrochaetae similar to feeding with methoxyacetic acid (MAA), the oxidation product of 2-ME. Larval feeding with 2-ME also affected the fertility of both females and males. 2-ME or more likely its intermediate oxidation product, methoxyacetaldehyde (MAALD), concurrently generated mutations in the premeiotic stages of the oocytes in the early third instar larvae. The mutagenicity of 2-ME has been confirmed in subsequent small scale experiments. The mutation frequency ranged from 4 x 10(-4) to 1 x 10(-2). Although terata were not supposed to be heritable, 1.1 to 8.7% of the affected females produced offspring with phenotypic similarity to the female parent. This phenomenon looked like a classical example of inheritance of an acquired character. The question is addressed why a Notch-like phenocopy, generated by larval 2-ME treatment, could bring forth Notch and rudimentary mutants in particular. Administration of 2-ME to larvae, containing the highly active alcohol dehydrogenase variant ADH-71k, exposed the mitotic germ cells and the mitotic somatic cells of the imaginal discs simultaneously to the mutagen MAALD and the teratogen MAA, respectively. The chances for specific gene mutations, though non-adaptive, were likely increased by a feedback mechanism: gene-products that were inhibited or disturbed by the teratogen demanded increased transcription of their encoding genes. Transcribed genes are more susceptible to mutagens.
Eisses
K T
KT
Biochemical Institute, University of Oslo, Norway. kteisses@dds.nl
D000014:Abnormalities, Drug-Induced / Q000235:genetics*; D000818:Animals; D004331:Drosophila melanogaster / Q000187:drug effects* / Q000196:embryology; D005026:Ethylene Glycols / Q000494:pharmacology*; D005260:Female; D008954:Models, Biological; D016296:Mutagenesis; D009153:Mutagens / Q000494:pharmacology*; D010641:Phenotype; D012098:Reproduction / Q000187:drug effects; D013723:Teratogens / Q000494:pharmacology*; D014921:Wings, Animal / Q000187:drug effects
D005026:Ethylene Glycols; D009153:Mutagens; D013723:Teratogens; C005219:methyl cellosolve