Ranganathan S, Davis D G, Leeper J D, Hood R D
Department of Biology, University of Alabama, Tuscaloosa 35487-1927.
Teratology. 1987 Dec;36(3):329-34. doi: 10.1002/tera.1420360309.
The role of alcohol dehydrogenase (ADH) activity in ethanol toxicity was investigated in Drosophila melanogaster. Flies from three congenic Adh strains (high, medium, and low ADH activity) were allowed to deposit eggs on medium containing 0, 4, or 8% ethanol. The resulting larvae were allowed to complete their development in the medium, and emerging flies were examined for defects. Flies with high ADH activity had malformation incidences of 0.8, 2.4, and 5.2% at 0, 4, and 8% ethanol, respectively. The comparable incidences for the low ADH strain were 1.0, 4.1, and 8.4%, while those for the medium ADH strain were intermediate in value. These results indicate that ethanol teratogenesis may be inversely related to ADH activity. When larvae were treated with ethanol for different lengths of time during development, the incidence of defects in flies from the high ADH strain was 3.9% when exposure started at the first instar and 3.09% when exposure started at the third instar. Results of the same exposures for the intermediate ADH strain were 5.2 and 3.4%, respectively, while those for the low ADH strain were 6.9 and 5.5%, respectively. Thus, length of ethanol exposure was directly related to the increased incidence of malformations in all tested Drosophila strains. For all tested strains, defect incidences appeared to be dose-related as well, regardless of length of exposure. ADH in Drosophila has a dual function and thus can catalyze oxidation of both ethanol and its toxic metabolite, acetaldehyde. This suggests that ethanol is the proximate teratogen in Drosophila.
在黑腹果蝇中研究了乙醇脱氢酶（ADH）活性在乙醇毒性中的作用。让来自三种同基因Adh品系（高、中、低ADH活性）的果蝇在含有0%、4%或8%乙醇的培养基上产卵。使所得幼虫在该培养基中完成发育，并检查羽化出的果蝇是否有缺陷。具有高ADH活性的果蝇在0%、4%和8%乙醇条件下的畸形发生率分别为0.8%、2.4%和5.2%。低ADH品系的相应发生率分别为1.0%、4.1%和8.4%，而中ADH品系的发生率介于两者之间。这些结果表明，乙醇致畸作用可能与ADH活性呈负相关。当幼虫在发育过程中用乙醇处理不同时间时，高ADH品系的果蝇在一龄开始暴露时的缺陷发生率为3.9%，在三龄开始暴露时为3.09%。中ADH品系相同暴露的结果分别为5.2%和3.4%，而低ADH品系的结果分别为6.9%和5.5%。因此，乙醇暴露时间与所有测试果蝇品系中畸形发生率的增加直接相关。对于所有测试品系，无论暴露时间长短，缺陷发生率似乎也与剂量相关。果蝇中的ADH具有双重功能，因此可以催化乙醇及其有毒代谢产物乙醛的氧化。这表明乙醇是果蝇中的直接致畸原。
